MULTIVALENT MACROLIDE ANTIBIOTICS

Abstract: Disclosed are multibinding compounds which include macrolide antibiotics, aminoglycosides, lincosamides, oxazolidinones, streptogramins, tetracycline and/or other compounds which bind to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium, which are useful in treating bacterial infections. The compounds adversely affect protein expression and have an antibacterial effect. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is macrolide antibiotic, aminoglycoside, lincosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA and/or one or more proteins involved in ribosomal protein synthesis in the bacterium.

Description: MULTIVALENT MACROLIDE ANTIBIOTICS CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application Serial Nos. 60/088,448 filed June 8, 1998 and 60/093,072 filed July 16, 1998 both of which are incorporated herein by reference in their entirety. BACKGROUND OF THE INVENTION Field of the Invention This invention relates to novel multibinding compounds (agents) that are macrolide antibiotics, aminoglycosides, lincosamides, oxazolidinones, strepto- gramins, tetracyclines or other compounds which bind to bacterial ribosomal RNA or one or more proteins involved in ribosomal protein synthesis in the bacterium, and to pharmaceutical compositions comprising such compounds. The compounds are useful as antibacterial agents for treating a variety of bacterial infections. State of the Art Organisms generate polypeptides (proteins) in order to survive. Organisms that cannot generate proteins cannot maintain viability. Because the majority of genes encode proteins, "gene expression" is nearly synonymous with protein synthesis. Gene expression involves two steps - transcription and translation. Genes code for proteins using various codons (units of three nucleotides), such as start codons (which initiate translation), stop codons (which stop translation) and codons in between the start and stop codons which selectively code for the various amino acids. Translation is the RNA directed synthesis of polypeptides. This process requires all three classes of RNA. The template for correct addition of individual amino acids is the mRNA, yet both tRNAs and rRNAs are involved in the process. Prokaryotes and eukaryotes use ribosomes to generate proteins. Ribosomes are cytoplasmic organelles, and are large complexes of proteins and three (prokaryotes) or four (eukaryotes) rRNA (ribosomal ribonucleic acid) molecules called subunits made in the nucleolus. Ribosomes serve as the site of mRNA translation. Once the two (large and small) subunits are joined by the mRNA from the nucleus, the ribosome translates the mRNA into a specific sequence of amino acids, or a polypeptide chain. In its inactive state, the ribosome exists as two subunits; a large subunit and a small subunit. When the small subunit encounters an mRNA, the process of translation of the mRNA to protein begins. There are two sites in the large subunit. for subsequent amino acid-charged tRNAs to bind to and thus be close enough to each other for the formation of a peptide bond. The A site accepts a new tR A bearing an amino acid, and the P site bears the tRNA attached to the growing chain. tRNA (transfer RNA) is a specific RNA molecule which acts as a translator between mRNA and protein. Each tRNA has a specific anticodon and acceptor site. Each tRNA also has a specific charger protein; this protein can only bind to that particular tRNA and attach the coπect amino acid to the acceptor site. The energy to make this bond comes from ATP. These charger proteins are called aminoacyl tRNA synthetases The tRNAs carry activated amino acids into the ribosome. The ribosome is associated with the mRNA ensuring coπect access of activated tR As and containing the necessary enzymatic activities to catalyze peptide bond formation. Protein synthesis proceeds from the N-terminus to the C-terminus of the protein. The ribosomes "read" the mRNA in the 5' to 3' direction. Active translation occurs on polyribosomes (also termed polysomes). This means that more than one ribosome can be bound to and translate a given mRNA at any one time. Chain elongation occurs by sequential addition of amino acids to the C- terminal end of the ribosome bound polypeptide. Translation proceeds in an ordered process. First accurate and efficient initiation occurs, then chain elongation and finally accurate and efficient termination must occur. All three of these processes require specific proteins, some of which are ribosome associated and some of which are separate from the ribosome, but may be temporaπh associated w ith it nitiation of Translation Before translation occurs, a πbosome must dissociate into its 30S and 50S subunits A ternary complex termed the preinitiation complex is formed consisting of the initiator, GTP, elF-2 and the 40S subunit The mRNA is bound to the preinitiation complex Initiation of translation in both prokaryotes and eukaryotes requires a specific initiator tRNA (which includes methionine) The initiation of translation requires recognition of a start (AUG) codon Peptide bond formation is catalyzed by a 23S rRNA component of the 50S subunit (peptidyl transferase) Another important site for protein synthesis is the 16S rRNA component of the 30S subunit (the aminoacyl tRNA site) When protein synthesis is terminated, release factor proteins bind to the stop codons, GTP hydrolysis occurs, and peptidyl transferase activity is stimulated, causing release of the protein from the tRNA Elongation of the New Protein After the first charged tRNA appears in the A site, the ribosome shifts so that the tRNA is in the P site New charged tRNAs, coπesponding to the codons of the mRNA, enter the A site, and a peptide bond is formed between the two amino acids The first tRNA is now released and the ribosome shifts again so that a tRNA carrying two ammo acids is now in the P site, and a new charged tRNA can bind to the A site. This process of elongation continues until the ribosome reaches a stop codon. Elongation requires specific non-ribosomal proteins. Elongation of polypeptides occurs in a cyclic manner. At the end of one complete round of amino acid addition the A site will be empty and ready to accept the incoming aminoacyl-tRNA dictated by the next codon of the mRNA. This means that not only does the incoming amino acid need to be attached to the peptide chain but the ribosome must move down the mRNA to the next codon. Each incoming aminoacyl-tRNA is brought to the ribosome by an eEF-l a-GTP complex. When the coπect tRNA is deposited into the A site the GTP is hydrolyzed and the eEF- la-GDP complex dissociates. For additional translocation events to occur the GDP must be exchanged for GTP. This is carried out by eEF-l bg similarly to the GTP exchange that occurs with elF-2 catalyzed by eIF-2B. The peptide attached to the tRNA in the P site is transfeπed to the amino group at the aminoacyl-tRNA in the A site. This reaction is catalyzed by peptidyltransferase in a process termed transpeptidation. The elongated peptide now resides on a tRNA in the A site. The A site needs to be freed in order to accept the next aminoacyl-tRNA. The process of moving the peptidyl-tRNA from the A site to the P site is termed, translocation. Translocation is catalyzed by eEF-2 coupled to GTP hydrolysis. In translocation, the ribosome is moved along the mRNA such that the next codon of the mRNA resides under the A site. Following translocation, eEF-2 is released from the ribosome and the cycle can start over again. Termination of the Protein When the ribosome reaches a stop codon, no aminoacyl tRNA binds to the empty A site. This signals the ribosomes to break into its large and small subunits, releasing the new protein and the mRNA. The protein may then undergo post- translational modifications. For example, it might be cleaved by a proteolytic (protein-cutting) enzyme at a specific place, have some of its amino acids altered, or become phosphorylated or glycosylated. Protein Synthesis Inhibitors In bacteπa, if the πbosomal RNA is inactivated, for example, through binding of a ligand to the πbosomal RNA, protein synthesis is ad\ ersel\ affected and the bacteπa will likely die Many of the antibiotics, in particular, MLS antibiotics, used to treat bacteπal infections function by inhibiting translation Inhibition can be effected at all stages of translation, from initiation to elongation to termination Many antibiotics are believed to pπmaπly attach to the ribosomal RNA at the 16S and 23S ribosomal subunits and inhibit growth of bacteria b\ inhibiting protein synthesis Chloramphenicol inhibits prokaryotic peptidyl transferase Streptomvcin and neomycin inhibit prokaryotic peptide chain initiation, also induce mRλ A misreading Tetracycline inhibits prokaryotic aminoacyl-tRNA binding to the ribosome small subunit Erythromycin inhibits prokaryotic translocation through the ribosome large subunit, and fusidic acid functions in a manner similar to erythromycin MLS antibiotics such as erythromycin have been used for years to treat vaπous infections, for example, those caused by gram positive bacteria, gram negative bacteria and anaerobic bacteπa Many bacteπa are becoming drug resistant One theory of how the bacteria become dmg resistant is that their πbosomal RNA mutates such that the antibiotics no longer bind as ligands to the RNA A number of macrolide antibiotics are orally bioavailable, but in contact with the gastrointestinal tract, degrade to some degree to form products hich cause adverse side effects such as diaπhea For this reason, many es ot naturally occurπng macrolide antibiotics such as erythromycin are esteπfied at the 6-posιtιon to minimize formation of the degradation products following oral administration It would be adv antageous to provide agents useful as antibiotics which ha\ e higher bioavailability, and are less subject to degradation and w hich ha\ e improved affinity for πbosomal R A The present ention prov ides such agents SUMMARY OF THE INVENTION This invention is directed to novel multibinding compounds (agents) that are macrolide antibiotics, aminoglycosides, hncosamides, oxazohdinones, streptogramins, tetracychnes or other compounds which bind to πbosomal RNA and/or to one or more proteins ιn\ olved in ribosomal protein s\ nthesis in the bacterium The multibinding compounds of this invention are useful as antibacteπals, in particular, for gram posιtι\ e, gram negatn e and anaerobic bacteπa Accordingly, in one of its composition aspects, this ention provides a multibinding compound comprising from 2 to 10 ligands covalently attached to one or more linkers wherein each of said ligands independently comprises a macrolide antibiotic, aminoglycoside, hncosamide, oxazolidinone, streptogramm, tetracycline or other compound which binds to ribosomal RNA and/or to one or more proteins involved in πbosomal protein synthesis in the bactenum and adversely affects protein synthesis, and pharmaceutically-acceptable salts thereof In another of its composition aspects, this invention prov ides a multibinding compound of formula I (L) p (X) q I wherein each L is independently a ligand comprising a macrolide antibiotic, aminoglycoside, hncosamide, oxazolidinone, streptogramm, tetracycline or other compound which binds to ribosomal RNA and/or to one or more proteins involved in πbosomal protein synthesis in the bactenum, each X is independently a linker, p is an integer of from 2 to 10; and q is an integer of from 1 to 20; and pharmaceutically-acceptable salts thereof. Preferably, q is less than/? in the multibinding compounds of this invention. Preferably, each ligand, L, in the multibinding compound of formula I is independently selected from the group consisting of erythromycin and ester prodrugs/derivatives thereof, such as erythromycin stearate and erythromycin estolate; clarithromycin, roxythromycin, azithromycin, aureomycin, oleandomycin. sulfisoxazole, spiramycin, troleandomycin, josamycin, cytovaricin, linezolid, eperezolid, clindamycin [AntirobeR], lincomycin, quinupristin, dalfopristin (Synercid, Rhone-Poulenc Rorer), streptomycin, amikacin, gentamicin, kanamycin, neomycin, tobramycin, netilmicin, paromomycin, tetracycline, chlortetracycline, doxyeycline, minocycline, declomycin, methacycline, spectinomycin, and oxytetracycline, and analogues thereof, which are well known to those of skill in the art. Examples of suitable analogues include alkylated, esterified, amidated, alkoxylated, sulfonated, carboxylated, halogenated, phosphorylated, thiolated and hydroxylated analogues. In still another of its composition aspects, this invention provides a multibinding compound of formula II: L'- X'- L' II wherein each L' is independently a ligand comprising a macrolide antibiotic, aminoglycoside, hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium and X' is a linker; and pharmaceutically-acceptable salts thereof. Preferably, in the multibinding compound of formula II, each ligand, L\ is independently selected from the group consisting of macrolide antibiotics, oxazohdmones, hncosamides. streptogramms, tetracychnes and aminoglycosides and X' is a linker, and pharmaceutically-acceptable salts thereof Preferably, in the abov e embodiments, each linker (1 e , X. X " or X") independently has the formula -X a -Z-(Y a -Z) m -Y b -Z-X a - wherein m is an integer of from 0 to 20 X a at each separate occuπence is selected from the group consisting of -0-, -S-, -NR-, -C(O)-, -C(0)0-, -C(0)NR-, -C(S), -C(S)0-, -C(S)NR- or a covalent bond where R is as defined below, Z is at each separate occuπence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, or a covalent bond, Y and Y b at each separate occuπence are selected from the group consisting of -C(0)NR\ -NR'C(O)-. -NR'C(0)NR'-, -C(=NR')-NR'-, -NR'-C(=NR , -NR'-C(0)-0-, -N=C(X a )-NR'-, -P(0)(OR')-0-, -S(0) n CR'R"-, -S(0) n -NR'-, -S-S- and a covalent bond, where n is 0, 1 or 2, and R, R' and R" at each separate occuπence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic In yet another of its composition aspects, this invention provides a pharmaceutical composition compnsing a pharmaceutically acceptable earner and an effective amount of a multibinding compound compnsing from 2 to 10 ligands covalently attached to one or more linkers wherein each of said ligands independently comprises a macrolide antibiotic, aminoglycoside, hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium, and pharmaceutically-acceptable salts thereof. This invention is also directed to pharmaceutical compositions comprising a pharmaceutically acceptable carrier and an effective amount of a multibinding compound of formula 1 or II. The multibinding compounds of this invention are effective antibiotics. Accordingly, in one of its method aspects, this invention provides a method for treating bacterial infections. When used to treat bacterial infections, for example, the method involves administering to a patient having a bacterial infection a pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a therapeutically-effective amount of a multibinding compound comprising from 2 to 10 ligands covalently attached to one or more linkers wherein each of said ligands independently comprises a macrolide antibiotic, aminoglycoside, hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium; and pharmaceutically-acceptable salts thereof. This invention is also directed to general synthetic methods for generating large libraries of diverse multimeric compounds which multimeric compounds are candidates for possessing multibinding properties with respect to ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium. The diverse multimeric compound libraries provided by this invention are synthesized by combining a linker or linkers with a ligand or ligands to provide for a library of multimeric compounds wherein the linker and ligand each have complementary functional groups permitting covalent linkage. The library of linkers is preferably selected to have diverse properties such as valency, linker length, linker geometry and rigidity, hydrophilicity or hydrophobicity. amphiphilicity, acidity, basicity and polarization. The library of ligands is preferably selected to have diverse attachment points on the same ligand. different functional groups at the same site of otherwise the same ligand, and the like. This invention is also directed to general synthetic methods for generating large libraries of diverse multimeric compounds which multimeric compounds are candidates for possessing multibinding properties with respect to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium. The diverse multimeric compound libraries provided by this invention are synthesized by combining a linker or linkers with a ligand or ligands to provide for a library of multimeric compounds wherein the linker and ligand each have complementary functional groups permitting covalent linkage. The library of linkers is preferably selected to have diverse properties such as valency, linker length, linker geometry and rigidity, hydrophilicity or hydrophobicity, amphiphilicity, acidity, basicity and polarizability and/or polarization. The library of ligands is preferably selected to have diverse attachment points on the same ligand, different functional groups at the same site of otherwise the same ligand, and the like. This invention is also directed to libraries of diverse multimeric compounds which multimeric compounds are candidates for possessing multibinding properties with respect to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium. These libraries are prepared via the methods described above and permit the rapid and efficient evaluation of what molecular constraints impart multibinding properties to a ligand or a class of ligands targeting the bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium. Accordinglv . in one of its method aspects, this inv ention is directed to a method for identifying multimenc ligand compounds possessing multibinding properties with respect to bacterial nbosomal RNA and or to one or more proteins involved in πbosomal protein synthesis in the bacterium hich method compnses (a) identifying a ligand or a mixture of ligands which bind to bactenal nbosomal RNA and/or to one or more proteins involved in nbosomal protein synthesis in the bactenum wherein each ligand contains at least one reactive functionality, (b) identifying a library of linkers wherein each linker in said library compnses at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand, (c) prepanng a multimenc ligand compound library by combining at least two stoichiometnc equivalents of the hgand or mixture of ligands identified in (a) with the library of linkers identified in (b) under conditions wherein the complementary functional groups react to form a covalent linkage between said linker and at least two of said ligands, and (d) assaying the multimenc ligand compounds produced in (c) above to identify multimenc ligand compounds possessing multibinding properties In another of its method aspects, this invention is directed to a method for identifying multimenc ligand compounds possessing multibinding properties which method compnses (a) identifying a library of ligands which bind to bactenal πbosomal RNA and/or to one or more proteins involved in nbosomal protein synthesis m the bactenum wherein each ligand contains at least one reactiv e functionality, (b) identifying a linker or mixture of linkers w herein each linker compnses at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand, (c) prepanng a multimenc ligand compound library by combining at least two stoichiometric equivalents of the library of ligands identified in (a) with the linker or mixture of linkers identified m (b) under conditions wherein the complementary functional groups react to form a cov alent linkage between said linker and at least two of said ligands. and (d) assaying the multimenc ligand compounds produced in (c) above to identify multimenc ligand compounds possessing multibinding properties The preparation of the multimenc ligand compound library is achieved bv either the sequential or concuπent combination of the two or more stoichiometric equivalents of the ligands identified in (a) with the linkers identified in (b) Sequential addition is prefeπed when a mixture of different ligands is employed to ensure heteromenc or multimenc compounds are prepared Concuπent addition ol the ligands occurs when at least a portion of the multimer comounds prepared are homomultimenc compounds The assay protocols recited in (d) can be conducted on the multimenc ligand compound library produced in (c) above, or preferably, each member-of the library is isolated by preparative liquid chromatography mass spectrometry (LCMS) In one of its composition aspects, this invention is directed to a library of multimenc ligand compounds which may possess multivalent properties which library is prepared by the method compnsing (a) identifying a ligand or a mixture of ligands which bind to bacterial πbosomal RNA and/or to one or more proteins involved in nbosomal protein synthesis in the bactenum wherein each hgand contains at least one reactive functionality, (b) identifying a hbrary of linkers wherein each linker in said library compnses at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the hgand, and (c) prepanng a multimenc ligand compound library by combining at least two stoichiometric equivalents of the ligand or mixture of ligands identified in (a) with the library of linkers identified in (b) under conditions wherein the complementary functional groups react to form a covalent linkage between said linker and at least two of said ligands In another of its composition aspects, this invention is directed to a library of multimenc ligand compounds which bind to bacterial πbosomal RNA and/or to one or more proteins mvolv ed in nbosomal protein synthesis in the bacterium which may possess multiv alent properties which library is prepared bv the method compnsing (a) identifying a library of ligands which bind to bacterial nbosomal RNA and/or to one or more proteins involved in nbosomal protein synthesis in the bactenum wherein each ligand contains at least one reactive functionality, (b) identifying a linker or mixture of linkers wherein each linker compnses at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand, and (c) prepanng a multimenc ligand compound library by combining at least two stoichiometπc equivalents of the library of ligands identified in (a) with the linker or mixture of linkers identified in (b) under conditions wherein the complementary functional groups react to form a covalent linkage between said linker and at least two of said ligands In a prefeπed embodiment, the library of linkers employed in either the methods or the library aspects of this invention is selected from the group compnsing flexible linkers, ngid linkers, hydrophobic linkers, hydrophilic linkers, linkers of different geometry, acidic linkers, basic linkers, linkers of different polanzabihty and/or polanzation and amphiphihc linkers For example, in one embodiment, each of the linkers in the linker library may comprise linkers of different chain length and/or having different complementary reactive groups Such linker lengths can preferably range from about 2 to 100A In another prefeπed embodiment, the hgand or mixture of ligands is selected to have reactive functionality at different sites on the ligands in order to provide for a range of onentations of said ligand on said multimenc ligand compounds. Such reactive functionality includes, by way of example, carboxylic acids, carboxylic acid halides, carboxyl esters, amines, halides, pseudohalides, isocyanates, vinyl unsaturation, ketones, aldehydes, thiols, alcohols, anhydrides, boronates and precursors thereof. It is understood, of course, that the reactive functionality on the ligand is selected to be complementary to at least one of the reactive groups on the linker so that a covalent linkage can be formed between the linker and the ligand. In other embodiments, the multimeric ligand compound is homomeric (i.e.. each of the ligands is the same, although it may be attached at different points) or heteromeric (i.e., at least one of the ligands is different from the other ligands). In addition to the combinatorial methods described herein, this invention provides for an iterative process for rationally evaluating what molecular constraints impart multibinding properties to a class of multimeric compounds or ligands targeting bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium. Specifically, this method aspect is directed to a method for identifying multimeric ligand compounds possessing multibinding properties with respect to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium which method comprises: (a) preparing a first collection or iteration of multimeric compounds which is prepared by contacting at least two stoichiometric equivalents of the ligand or mixture of ligands which target bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium with a linker or mixture of linkers wherein said ligand or mixture of ligands comprises at least one reactive functionality and said linker or mixture of linkers comprises at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand wherein said contacting is conducted under conditions wherein the complementary functional groups react to form a covalent linkage between said linker and at least two of said ligands; -13- (b) assaying said first collection or iteration of multimenc compounds to assess which if any of said multimenc compounds possess multibinding properties, (c) repeating the process of (a) and (b) abo e until at least one multimenc compound is found to possess multibinding properties, (d) evaluating what molecular constraints imparted multibinding properties to the multimenc compound or compounds found in the first iteration recited in (a)- (c) above, (e) creating a second collection or iteration of multimenc compounds which elaborates upon the particular molecular constraints imparting multibinding properties to the multimenc compound or compounds found in said first iteration, (f) evaluating what molecular constraints imparted enhanced multibinding properties to the multimenc compound or compounds found in the second collection or iteration recited in (e) above, (g) optionally repeating steps (e) and (f) to further elaborate upon said molecular constraints Preferably, steps (e) and (f) are repeated at least two times, more preferably at from 2-50 times, even more preferably from 3 to 50 times, and still more preferably at least 5-50 times BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic illustration of representative macrolide antibiotics, aminoglycosides and Imcosamides, oxazohdmones, streptogramms, tetracycline hich can be used to prepare the compounds of the present invention Figures 2-20 are schematic illustrations of the preparation of compounds of formula 1-XIX, respectively Figure 21 is a schematic illustration of the preparation of compounds of formulas XXa, XXb and XXc Figures 22-24, 24a, 25, 25a, and 26-37 are schematic illustrations of the preparation of compounds of formula XXI-XXXVIII, respectively Figure 38 is a schematic illustration of the preparation of compounds of formulas XXXIX-A and XXXIX-B Figures 39-49 are schematic illustrations of the preparation of compounds of foπnula XL-L Figure 50 is a schematic illustration of the preparation of compounds of formulas LI-A and LI-B Figure 51 is a schematic illustration of the preparation of compounds of formulas LII-A and LII-B Figure 52 is a schematic illustration of the preparation of compounds of formula LIII-A and LIII-B Figures 53-55 are schematic illustrations of the preparation of compounds of formula LIV-LVI Figure 56 illustrates examples of multibinding compounds compnsing 2 ligands attached in different forms to a linker Figure 57 illustrates examples of multibinding compounds comprising 3 ligands attached in different forms to a linker Figure 58 illustrates examples of multibinding compounds comprising 4 ligands attached in different forms to a linker Figure 59 illustrates examples of multibinding compounds comprising between 5 and 10 ligands attached in different forms to a linker DETAILED DESCRIPTION OF THE INVENTION This invention is directed to multibinding compounds which are macrolide antibiotics, aminoglycosides, Imcosamides, oxazohdmones, streptogramms, tetracyclmes or other compounds which bind to bacterial ribosomal RNA and/or to one or more proteins involved in nbosomal protein synthesis in the bacterium, preferably in a manner which inhibits protein expression and results in an antibactenal activity, pharmaceutical compositions containing such compounds and methods of antibactenal treatment When discussing such compounds, compositions or methods, the following terms have the following meanings unless otherwise indicated Any undefined terms have their art recognized meanings The term "alkyl" refers to a monoradical branched or unbranched saturated hydrocarbon chain preferably having from 1 to 40 carbon atoms, more preferably 1 to 10 carbon atoms, and even more preferably 1 to 6 carbon atoms. This term is exemplified by groups such as methyl, ethyl, //-propyl, /so-propyl. /--butyl, iso- butyl, //-hexyl, /j-decyl, tetradecyl, and the like. The term "substituted alkyl" refers to an alkyl group as defined above, having from 1 to 5 substituents, and preferably 1 to 3 substituents, selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, keto, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -S0 2 -alkyl, -SO,-substituted alkyl, -S0 2 -aryl and -S0 2 -heteroaryl. The term "alkylene" refers to a diradical of a branched or unbranched saturated hydrocarbon chain, preferably having from 1 to 40 carbon atoms, more preferably 1 to 10 carbon atoms and even more preferably 1 to 6 carbon atoms. This term is exemplified by groups such as methylene (-CH 2 -), ethylene (-CH j CH,-), the propylene isomers (e.g., -CH 2 CH 2 CH 2 - and -CH(CH 3 )CH 2 -) and the like. The term "substituted alkylene" refers to an alkylene group, as defined above, having from 1 to 5 substituents. and preferably 1 to 3 substituents, selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, keto, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy. heterocyclic, heterocyclooxy. hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl. -SO-aryl, - SO-heteroaryl, -S0 2 -alkyl, -S0 -substituted alkyl, -S0 2 -aryl and -SO : -heteroaryl. Additionally, such substituted alkylene groups include those where 2 substituents on the alkylene group are fused to form one or more cycloalkyl. substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heterocyclic or heteroaryl groups fused to the alkylene group. Preferably such fused groups contain from 1 to 3 fused ring structures. The term "alkaryl" refers to the groups -alkylene-aryl and -substituted alkylene-aryl where alkylene. substituted alkylene and aryl are defined herein. Such alkaryl groups are exemplified by benzyl, phenethyl and the like. The term "alkoxy" refers to the groups alkyl-O-, alkenyl-O-. cycloalkyl-O-, cycloalkenyl-O-, and alkynyl-O-, where alkyl, alkenyl, cycloalkyl, cycloalkenyl, and alkynyl are as defined herein. Prefeπed alkoxy groups are alkyl-O- and include, by way of example, methoxy, ethoxy, //-propoxy, z ' so-propoxy, //-butoxy, tert-butoxy, sec-butoxy, //-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, and the like. The term "substituted alkoxy" refers to the groups substituted alkyl-O-, substituted alkenyl-O-, substituted cycloalkyl-O-, substituted cycloalkenyl-O-, and substituted alkynyl-O- where substituted alkyl, substituted alkenyl, substituted cycloalkyl, substituted cycloalkenyl and substituted alkynyl are as defined herein. The term "alkylalkoxy" refers to the groups -alkylene-O-alkyl, alkylene-O-substituted alkyl, substituted alkylene-O-alkyl and substituted alkylene-O-substituted alkyl wherein alkyl, substituted alkyl, alkylene and substituted alkylene are as defined herein. Prefeπed alkylalkoxy groups are alkylene-O-alkyl and include, by way of example, methylenemethoxy (-CH 2 OCH 3 ), ethylenemethoxy (-CH 2 CH 2 OCH 3 ), n-propylene-wo-propoxy (-CH 2 CH 2 CH 2 OCH(CH 3 ) 2 ), methylene-t-butoxy (-CH 2 -0-C(CH 3 ) 3 ) and the like. The term "alkylthioalkoxy" refers to the group -alkylene-S-alkyl, alkylene-S-substituted alkyl, substituted alkylene-S-alkyl and substituted alkylene- S-substituted alkyl wherein alkyl, substituted alkyl, alkylene and substituted alkylene are as defined herein. Prefeπed alkylthioalkoxy groups are alkylene-S- alkyl and include, by way of example, methylenethiomethoxy (-CH 2 SCH 3 ), ethylenethiomethoxy (-CH 2 CH 2 SCH 3 ), //-propylene-zPo-thiopropoxy (-CH 2 CH 2 CH 2 SCH(CH 3 ) 2 ), methylene-t-thiobutoxy (-CH 2 SC(CH 3 ) 3 ) and the like. The term "alkenyl" refers to a monoradical of a branched or unbranched unsaturated hydrocarbon group preferably having from 2 to 40 carbon atoms, more preferably 2 to 10 carbon atoms and even more preferably 2 to 6 carbon atoms and having at least 1 and preferably from 1-6 sites of vinyl unsaturation. Prefeπed alkenyl groups include ethenyl (-CH=CH 2 ), //-propenyl (-CH 2 CH=CH 2 ), wo-propenyl (-C(CH 3 )=CH 2 ), and the like. The term "substituted alkenyl" refers to an alkenyl group as defined above having from 1 to 5 substituents, and preferably 1 to 3 substituents, selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, keto, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -S0 2 -alkyl, -SO,-substituted alkyl, -S0 2 -aryl and -S0 2 -heteroaryl. The term "alkenylene" refers to a diradical of a branched or unbranched unsaturated hydrocarbon group preferably having from 2 to 40 carbon atoms, more preferably 2 to 10 carbon atoms and even more preferably 2 to 6 carbon atoms and having at least 1 and preferably from 1-6 sites of vinyl unsaturation. This term is exemplified by groups such as ethenylene (-CH " =CH-), the propenylene isomers (e.g., -CH 2 CH=CH- and -C(CH ; ,)=CH-) and the like. The term "substituted alkenylene" refers to an alkenylene group as defined above having from 1 to 5 substituents, and preferably from 1 to 3 substituents, selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, keto. thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, - SO-heteroaryl, -S0 2 -alkyl, -SO,-substituted alkyl, -S0 2 -aryl and -S0 2 -heteroaryl. Additionally, such substituted alkenylene groups include those where 2 substituents on the alkenylene group are fused to form one or more cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heterocyclic or heteroaryl groups fused to the alkenylene group. The term "alkynyl" refers to a monoradical of an unsaturated hydrocarbon preferably having from 2 to 40 carbon atoms, more preferably 2 to 20 carbon atoms and even more preferably 2 to 6 carbon atoms and having at least 1 and preferably from 1-6 sites of acetylene (triple bond) unsaturation. Prefeπed alkynyl groups include ethynyl (-C≡CH), propargyl (-CH 2 C≡CH) and the like. The term "substituted alkynyl" refers to an alkynyl group as defined above having from 1 to 5 substituents, and preferably 1 to 3 substituents, selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, keto, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO-,-alkyl. -S0 2 -substituted alkyl, -S0 2 -aryl and -S0 2 -heteroaryl. The term "alkynylene" refers to a diradical of an unsaturated hydrocarbon preferably having from 2 to 40 carbon atoms, more preferably 2 to 10 carbon atoms and even more preferably 2 to 6 carbon atoms and having at least 1 and preferably from 1 -6 sites of acetylene (triple bond) unsaturation. Prefeπed alkynylene groups include ethynylene (-C≡C-), propargylene (-CP C≡C-) and the like. The term "substituted alkynylene" refers to an alkynylene group as defined above having from 1 to 5 substituents, and preferably 1 to 3 substituents, selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, keto, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, - SO-heteroaryl, -S0 2 -alkyl, -S0 2 -substituted alkyl, -S0 2 -aryl and -S0 2 -heteroaryl The term "acyl" refers to the groups HC(O)-, alkyl-C(O)-, substituted alky - C(O)-, cycloalkyl-C(O)-, substituted cycloalkyl-C(O)-, cycloalkenyl-C(O)-, substituted cycloalkenyl-C(O)-, aryl-C(O)-, heteroaryl-C(O)- and heterocyclic- C(O)- where alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic are as defined herein. The term "acylamino" or "aminocarbonyl" refers to the group -C(0)NRR where each R is independently hydrogen, alkyl, substituted alkyl, aryl. heteroaryl, heterocychc or where both R groups are joined to form a heterocyclic group (e g morpholino) wherein alkyl, substituted alk l, ar l, heteroaryl and heterocvc c are as defined herein The term "aminoacyl" refers to the group -NRC(0)R where each R is independently hydrogen, alkyl, substituted alkyl, aryl, heteroaryl, or heterocvchc wherein alkyl, substituted alkyl, aryl, heteroaryl and heterocyclic are as defined herein The term "aminoacyloxy" or "alkoxy carbonylamino" refers to the gioup -NRC(0)OR where each R is hydrogen, alkyl, substituted alkv 1, aryl, heteroaryl, or heterocyclic wherein alkyl, substituted alkyl, aryl, heteroaryl and heterocyclic are as defined herein The term "acyloxy" refers to the groups alkyl-C(0)0-, substituted alkvl- C(0)0-, cycloalkyl-C(0)0-, substituted cycloalkyl-C(0)0-, aryl-C(0)0-, heteroaryl-C(0)0-, and heterocychc-C(0)0- wherein alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, heteroaryl, and heterocyclic are as defined herein The term "aryl" refers to an unsaturated aromatic carbocychc group of irom 6 to 20 carbon atoms having a single ring (e g , phenyl) or multiple condensed (fused) nngs (e.g., naphthyl or anthryl) Prefeπed aryls include phenvl, naphthyl Unless otherwise constrained by the definition for the aryl substituent. such aryl groups can optionally be substituted with from 1 to 5 substituents, pre fei ably 1 to 3 substituents, selected from the group consisting of acyloxy, hydroxy, thiol, acyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, substituted alk l, substituted alkoxy, substituted alkenyl, substituted alkynyl, substituted cycloalkyl, substituted cycloalkenyl, amino, substituted amino, aminoacyl, acylamino, alkaryl, aryl, aryloxy, azido, carbox l. carboxylalkyl, cyano, halo, nitro, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, aminoacylox . oxyacylamino, thioalkoxy, substituted thioalkoxy, thioaryloxy, thioheteroaryloxv , -SO-alkyl, -SO- substituted alkyl, -SO-aryl, -SO-heteroaryl, -S0 2 -alkyl, -S0 -substituted alkyl, - S0 2 -aryl, -S0 2 -heteroaryl and tπhalomethyl. Prefeπed arv 1 substituents include alkyl, alkoxy, halo, cyano, nitro, tπhalomethyl, and thioalkoxy The term "aryloxy" refers to the group aryl-O- wherein the aryl group is as defined above including optionally substituted aryl groups as also defined above The term "arylene" refers to the diradical denved from aryl (including substituted aryl) as defined above and is exemplified by 1 ,2-phenylene, 1,3- phenylene, 1 ,4-phenylene, 1,2-naphthylene and the like The term "amino" refers to the group -NH 2 The term "substituted amino refers to the group -NRR where each R is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl. substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic provided that both R's are not hydrogen. The term "carboxyalkyl" or "alkoxycarbonyl" refers to the groups "-C(0)0-alkyl", "-C(0)0-substιtuted alkyl", "-C(0)0-cycloalkyl", "-C(0)O- substituted cycloalkyl", "-C(0)0-alkenyl", "-C(0)0-substituted alkenyl", "-C(0)0-alkynyl" and "-C(0)0-substituted alkynyl" where alkyl, substituted alkyl. cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl and substituted alkynyl alkynyl are as defined herein The term "cycloalkyl" refers to cyclic alkyl groups of from 3 to 20 carbon atoms having a single cyclic πng or multiple condensed nngs Such cycloalkyl groups include, by way of example, single ring stmctures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl, and the like, or multiple ring stmctures such as adamantanyl, and the like. The term "substituted cycloalkyl" refers to cycloalkyl groups having from 1 to 5 substituents, and preferably 1 to 3 substituents, selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, keto, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -S0 2 -alkyl, -S0 2 -substituted alkyl, -S0 2 -aryl and -S0 2 -heteroaryl. The term "cycloalkenyl" refers to cyclic alkenyl groups of from 4 to 20 carbon atoms having a single cyclic ring and at least one point of internal unsaturation. Examples of suitable cycloalkenyl groups include, for instance, cyclobut-2-enyl, cyclopent-3-enyl, cyclooct-3-enyl and the like. The term "substituted cycloalkenyl" refers to cycloalkenyl groups having from 1 to 5 substituents, and preferably 1 to 3 substituents, selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, keto, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl. -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -S0 2 -alkyl, -S0 2 -substituted alkyl, -S0 2 -aryl and -S0 2 -heteroaryl. The term "halo" or "halogen" refers to fluoro, chloro, bromo and iodo. The term "heteroaryl" refers to an aromatic group of from 1 to 15 carbon atoms and 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur within at least one ring (if there is more than one ring). Unless otherwise constrained by the definition for the heteroaryl substituent, such heteroaryl groups can be optionally substituted with 1 to 5 substituents, preferably 1 to 3 substituents, selected from the group consisting of acyloxy, hydroxy, thiol, acyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, substituted alkyl, substituted alkoxy, substituted alkenyl, substituted alkynyl, substituted cycloalkyl, substituted cycloalkenyl, amino, substituted amino, aminoacyl, acylamino, alkaryl, aryl, aryloxy, azido, carboxyl, carboxylalkyl, cyano, halo, nitro, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, aminoacyloxy, oxyacylamino, thioalkoxy, substituted thioalkoxy, thioaryloxy, thioheteroaryloxy, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, - SO,-alkyl, -S0 2 -substituted alkyl, -S0 2 -aryl, -S0 2 -heteroaryl and trihalomethyl. Prefeπed aryl substituents include alkyl, alkoxy, halo, cyano, nitro, trihalomethyl, and thioalkoxy. Such heteroaryl groups can have a single ring (e.g., pyridyl or furyl) or multiple condensed rings (e.g., indolizinyl or benzothienyl). Prefeπed heteroaryls include pyridyl, pyπolyl and furyl. The term "heteroaryloxy" refers to the group heteroaryl-O-. The term "heteroarylene" refers to the diradical group derived from heteroaryl (including substituted heteroaryl), as defined above, and is exemplified by the groups 2,6-pyridylene, 2,4-pyridiylene, 1,2-quinolinylene, 1 ,8- quinolinylene, 1,4-benzofuranylene, 2,5-pyridnylene, 2,5-indolenyl and the like. The term "heterocycle" or "heterocyclic" refers to a monoradical saturated or unsaturated group having a single ring or multiple condensed rings, from 1 to 40 carbon atoms and from 1 to 10 hetero atoms, preferably 1 to 4 heteroatoms, selected from nitrogen, sulfur, phosphoms, and or oxygen w ithin the ring Unless otherwise constrained by the definition for the heterocyclic substituent, such heterocyclic groups can be optionally substituted with 1 to 5, and preferably 1 to 3 substituents, selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, keto, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy. thioheterocyclooxy, thiol. thioalkoxy, substituted thioalkoxy, aryl, aryloxy , heteroary l, heteroaryloxy, heterocyclic. heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl, -SO- substituted alkyl, -SO-aryl, -SO-heteroaryl, -S0 2 -alkyl, -S0 2 -substituted alkyl, - S0 2 -aryl and -S0 2 -heteroaryl. Such heterocyclic groups can have a single ring or multiple condensed nngs. Prefeπed heterocyclics include morpholino, piperidinyl, and the like Examples of nitrogen heterocycles and heteroaryls include, but are not limited to, pyπole, imidazole, pyrazole, pyπdine, pyrazine, pynmidine, pyridazine, indolizine, isomdole, indole, mdazole, punne, quinolizme, isoquinohne, quinoline, phthalazine, naphthylpyndine, quinoxahne, qumazohne, cinnohne, ptendine, carbazole, carboline, phenanthridine, acridine, phenanthrohne, isothiazole, phenazine, isoxazole, phenoxazine, phenothiazine, lmidazolidine, lmidazohne. piperidine, piperazine, indoline, morpholino, pipendinyl, tetrahydro furanyl, and the like as well as N-alkoxy-mtrogen containing heterocycles The term "heterocyclooxy" refers to the group heterocychc-O- The term "thioheterocyclooxy" refers to the group heterocychc-S- The term "heterocyclene" refers to the diradical group formed from a heterocycle, as defined herein, and is exemplified by the groups 2,6-morpholino, 2,5-morpholino and the like. The term "oxyacylamino" or "aminocarbonyloxy" refers to the group -OC(0)NRR where each R is independently hydrogen, alkyl, substituted alkyl, aryl, heteroaryl, or heterocyclic wherein alkyl, substituted alkyl, aryl, heteroaryl and heterocyclic are as defined herein. The term "spiro-attached cycloalkyl group" refers to a cycloalkyl group attached to another ring via one carbon atom common to both rings. The term "thiol" refers to the group -SH. The term "thioalkoxy" refers to the group -S-alkyl. The term "substituted thioalkoxy" refers to the group -S-substituted alkyl. The term "thioaryloxy" refers to the group aryl-S- wherein the aryl group is as defined above including optionally substituted aryl groups also defined above. The term "thioheteroaryloxy" refers to the group heteroaryl-S- wherein the heteroaryl group is as defined above including optionally substituted aryl groups as also defined above. As to any of the above groups which contain one or more substituents, it is understood, of course, that such groups do not contain any substitution or substitution patterns which are sterically impractical and/or synthetically non- feasible. In addition, the compounds of this invention include all stereochemical isomers arising from the substitution of these compounds, whether the isomers are those arising in the ligands. the linkers, or the multiv alent constmcts including the ligands and linkers The term "pharmaceutically-acceptable salt" refers to salts hich retain the biological effectiveness and properties of the multibinding compounds of this invention and which are not biologically or otherwise undesirable In many cases, the multibinding compounds of this invention are capable of forming acid and/or base salts by virtue of the presence of amino and/or carboxy l groups or groups similar thereto Pharmaceutically-acceptable base addition salts can be prepared from inorganic and organic bases Salts denved from inorganic bases, include by way of example only, sodium, potassium, lithium, ammonium, calcium and magnesium salts Salts denved from organic bases include, but are not limited to, salts of pnmary, secondary and tertiary amines, such as alkyl amines, dialkyl amines, tπalkyl amines, substituted alkyl ammes, dι(substιtuted alkyl) amines, tπ(substιtuted alkyl) amines, alkenyl ammes, dialkenyl amines, tπalkenyl amines, substituted alkenyl amines, dι(substιtuted alkenyl) amines, tπ(substιtuted alkenyl) amines, cycloalkyl amines, dι(cycloalkyl) amines, tπ(cycloalkyl) ammes, substituted cycloalkyl amines, disubstituted cycloalkyl amine, tnsubstituted cycloalkyl amines, cycloalkenyl amines, dι(cycloalkenyl) amines, tn(cycloalkenyl) amines, substituted cycloalkenyl amines, disubstituted cycloalkenyl amine, tnsubstituted cycloalkenyl amines, aryl amines, diaryl amines, tπaryl amines, heteroaryl amines, diheteroaryl amines, tnheteroaryl amines, heterocyclic amines, diheterocychc amines, tnheterocychc amines, mixed di- and tπ-amines where at least two of the substituents on the amine are different and are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic, and the like Also included are ammes where the two or three substituents, together with the amino nitrogen, form a heterocyclic or heteroaryl group Examples of suitable amines include, by w ay of example only, isopropylamine, tnmethyl amine, diethyl amine, tn( * 5o-propyl) amine, tn(/z- propyl) amine, ethanolamine, 2-dιmethylamιnoethanol, tromethamine, lysine. arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, N-alkylglucamines, theobromine, punnes, piperazine, pipendme, morpholine, N-ethylpipeπdine, and the like It should also be understood that other carboxylic acid derivatives would be useful in the practice of this invention, for example, carboxylic acid amides, including carboxamides lower alkyl carboxamides, dialkyl carboxamides, and the like Pharmaceutically acceptable acid addition salts may be prepared from inorganic and organic acids Salts denved from inorganic acids include hydrochlonc acid, hydrobromic acid, sulfuπc acid, mtπc acid, phosphoπc acid, and the like Salts denved from organic acids include acetic acid, propiomc acid, glycohc acid, pymvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumanc acid, tartaπc acid, citnc acid, benzoic acid, cinnamic acid mandelic acid, methanesulfonic acid, ethanesuifonic acid, -toluene-sulfomc acid salicylic acid, and the like The term "pharmaceutically-acceptable cation" refers to the cation of a pharmaceutically-acceptable salt The term "protecting group" or "blocking group" refers to any group which when bound to one or more hydroxyl, thiol, amino or carboxyl groups of the compounds (including intermediates thereof) prevents reactions from occurring at these groups and which protecting group can be removed by conventional chemical or enzymatic steps to reestablish the hydroxyl, thiol, amino or carboxyl group The particular removable blocking group employed is not cntical and prefeπed removable hydroxyl blocking groups include conventional substituents such as allyl, benzyl, acetyl, chloroacetyl, thiobenzyl, benzylidme, phenacyl, t-butyl- diphenylsilyl and any other group that can be introduced chemically onto a hydroxyl functionality and later selectively removed either by chemical or enzymatic methods in mild conditions compatible with the nature of the product Prefeπed removable thiol blocking groups include disulfide groups, acyl groups, benzyl groups, and the like Prefeπed removable ammo blocking groups include conventional substituents such as t-butyoxycarbonyl (t-BOC), benzyloxycarbonyl (CBZ), fluorenylmethoxycarbonyl (FMOC), allyloxycarbonyl (ALOC), and the like which can be removed by conventional conditions compatible with the nature of the product. Prefeπed carboxyl protecting groups include esters such as methyl, ethyl, propyl, t-butyl etc. which can be removed by mild conditions compatible with the nature of the product. The term "optional" or "optionally" means that the subsequently described event, circumstance or substituent may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. The term "ligand" as used herein denotes a compound that binds to ribosomal RNA and/or to one or more proteins involved in nbosomal protein synthesis in the bactenum The specific region or regions of the hgand that is (are) recognized by the enzyme is designated as the "ligand domain" A ligand may be either capable of binding to an enzyme by itself, or may require the presence of one or more non-hgand components for binding (e.g., Ca "2 , Mg 2 or a water molecule is required for the binding of a ligand to vanous ligand binding sites) Examples of ligands useful in this invention are described herein General classes of compounds useful as ligands include macrolide antibiotics, oxazohdinones, Imcosamides, streptogramms. tetracyclmes and aminoglycosides Examples of macrolide antibiotics include erythromvcin and ester denvativ eb thereof, such as erythromycin stearate and erythromycin estolate, claπthromv cin. roxythromycin, azithromycin, streptomycin, aureomycin, oleandomycin, sulfisoxazole, spiramycin, troleandomycin, josamycin and cytovaπcin Examples of oxazohdmones include hnezohd and eperezohd Examples of Imcosamides include chndamycin [AntirobeR] and hncomycm Examples of streptogramms include quinupπstin and dalfopπstin (Synercid, Rhone-Poulenc Rorer) Examples of aminoglycosides include streptomycin, amikacin, gentamicin, kanamycin, neomycin, tobramycin, netilmicm and paromomycm Examples of tetracyclmes include tetracycline, chlortetracychne, doxyeycline, minocychne, declomycin, methacychne and oxytetracychne Those skilled in the art will appreciate that portions of the ligand stmcture that are not essential for specific molecular recognition and binding activity may be vaned substantially, replaced or substituted with unrelated structures (for example, with ancillary groups as defined below) and, in some cases, omitted entirely without affecting the binding interaction The primary requirement for a ligand is that it has a ligand domain as defined above It is understood that the term ligand is not intended to be limited to compounds known to be useful in binding to bactenal πbosomal RNA and/or to one or more proteins involved in nbosomal protein synthesis in the bactenum (e g , known dmgs) Those skilled in the art will understand that the term ligand can equally apply to a molecule that is not normally associated with bactenal nbosomal RNA binding properties In addition, it should be noted that ligands that exhibit marginal activity or lack useful activity as monomers can be highly active as multivalent compounds because of the benefits confeπed by multivalency The term "multibinding compound or agent" refers to a compound that is capable of multivalency, as defined below, and which has 2-10 ligands covalently bound to one or more linkers which may be the same or different Multibinding compounds provide a biological and/or therapeutic effect greater than the aggregate of unlinked ligands equivalent thereto which are made av ailable for binding That is to say that the biological and/or therapeutic effect of the ligands attached to the multibinding compound is greater than that achiev ed by the same amount of unlinked ligands made available for binding to the ligand binding sites (receptors) The phrase "increased biological or therapeutic effect" includes, for example * increased affinity, increased selectivity for target, increased specificity for target, increased potency, increased efficacy, decreased toxicity, improved duration of activity or action, decreased side effects, increased therapeutic index, improved bioavailability, improved pharmacokinetics, improved activity spectrum, and the like. The multibinding compounds of this invention w ill exhibit at least one and preferably more than one of the above-mentioned effects The term "potency" refers to the minimum concentration at which a ligand is able to achieve a desirable biological or therapeutic effect The potency of a ligand is typically proportional to its affinity for its ligand binding site In some cases, the potency may be non-hnearly coπelated with its affinity. In compaπng the potency of two dmgs, e.g., a multibinding agent and the aggregate of its unlinked ligand, the dose-response curve of each is determined under identical test conditions (e.g., in an in vitro or in vivo assay, in an appropnate animal model) The finding that the multibinding agent produces an equivalent biological or therapeutic effect at a lower concentration than the aggregate unlinked ligand is indicative of enhanced potency The term "univalency" as used herein refers to a single binding interaction between one ligand as defined herein with one ligand binding site as defined herein It should be noted that a compound having multiple copies of a ligand (or ligands) exhibit univalency when only one ligand is interacting with a ligand binding site. Examples of univalent interactions are depicted below The term "multivalency" as used herein refers to the concuπent binding of from 2 to 10 linked ligands (which may be the same or different) and two or more coπesponding receptors (ligand binding sites) on one or more bacterial ribosomes which may be the same or different. For example, two ligands connected through a linker that bind concuπently to two ligand binding sites would be considered as bivalency; three ligands thus connected would be an example of trivalency. An example of trivalent binding, illustrating a multibinding compound bearing three ligands versus a monovalent binding interaction, is shown below: Univalent Interaction Tnvalent Interaction It should be understood that all compounds that contain multiple copies of a ligand attached to a linker or to linkers do not necessanly exhibit the phenomena of multivalency, l e., that the biological and/or therapeutic effect of the multibinding agent is greater than the sum of the aggregate of unlinked ligands made av ilable for binding to the ligand binding site (receptor) For multivalency to occur, the ligands that are connected by a linker or linkers have to be presented to their ligand binding sites by the hnker(s) in a specific manner in order to bnng about the desired hgand-onenting result, and thus produce a multibinding event The term "selectivity" or "specificity" is a measure of the binding preferences of a ligand for different ligand binding sites (receptors) The selectivity of a ligand with respect to its target ligand binding site relative to another ligand binding site is given by the ratio of the respective values of K d (I e the dissociation constants for each hgand-receptor complex) or, in cases where a biological effect is observed below the K d , the ratio of the respective EC ) 's ( I e . the concentrations that produce 50% of the maximum response for the ligand interacting with the two distinct hgand binding sites (receptors)) The term "ligand binding site" denotes the site on the bacterial nbosomal RNA, which may be specific RNA and/or a site on one or more of the proteins involved in nbosomal protein synthesis in the bactenum that recognizes a ligand domain and provides a binding partner for the ligand. The ligand binding site may be defined by monomeric or multimeric stmctures. It should be recognized that the ligand binding sites of the ribosome that participate in biological multivalent binding interactions are constrained to varying degrees by their intra- and inter-molecular associations (e.g., such macromolecular stmctures may be covalently joined to a single stmcture, noncovalently associated in a multimeric stmcture, embedded in a membrane or polymeric matrix, and so on) and therefore have less translational and rotational freedom than if the same stmctures were present as monomers in solution. The term "inert organic solvent" means a solvent which is inert under the conditions of the reaction being described in conjunction therewith including, by way of example only, benzene, toluene, acetonitrile, tetrahydrofuran, dimethylformamide, chloroform, methylene chloride, diethyl ether, ethyl acetate, acetone, methylethyl ketone, methanol, ethanol, propanol, isopropanol, t-butanol, dioxane, pyridine, and the like. Unless specified to the contrary, the solvents used in the reactions described herein are inert solvents. The term "treatment" refers to any treatment of a pathologic condition in a mammal, particularly a human, and includes: (i) preventing the pathologic condition from occurring in a subject which may be predisposed to the condition but has not yet been diagnosed with the condition and, accordingly, the treatment constitutes prophylactic treatment for the disease condition; (ii) inhibiting the pathologic condition, i.e., aπesting its development; (iii) relieving the pathologic condition, i.e., causing regression of the pathologic condition; or (iv) relieving the conditions mediated by the pathologic condition. The term "pathologic condition which is modulated by treatment with a ligand" covers all disease states (1 e , pathologic conditions) which are generally acknowledged in the art to be usefully treated ith a ligand for the bactenal nbosomal RNA and/or for one or more proteins involved in nbosomal protein synthesis in the bactenum, in general, and those disease states which have been found to be usefully treated by a specific multibinding compound of our inv ention Such disease states include, by way of example only, the treatment of bacterial infections Examples of bactena which can be treated w ith the compositions and methods descnbed herein include gram-positiv e cocci, for example, staphylococci and streptococci, gram-positive rods such as corynebactena and diphtheroids, bacilli, mycobactena and Nocardia, gram-negative rods such as entenc gram-negative rods, Pseudomonas, curved gram-negative rods, parvobactena and Haemophύus, gram-negative cocci such as Neissena, obligate anaerobes such as Clostridium, non-sponng anaerobes, and unusual bacteπa such as spirochaetes, πckettsia and chlamydia Specific examples of bactenal diseases include chlamydia, gonoπhea, salmonellosis, shigellosis, tuberculosis, syphilis, bacterial pneumonia, bactenal sepsis, unnary tract infections, bactenal upper respiratory tract infections, otitis media, and lyme disease While not wishing to be bound to a particular theory, it is believed that the compounds descnbed herein inhibit growth of bacteria by binding to their 16S or 23S πbosomal subunits, or to one or more proteins present on the bactenal nbosome, and inhibiting protein synthesis The term "therapeutically effective amount" refers to that amount of multibinding compound which is sufficient to effect treatment, as defined abov e, when administered to a mammal in need of such treatment The therapeutically effective amount will vary depending upon the subject and disease condition being treated, the weight and age of the subject, the severity of the disease condition, the manner of administration and the like, which can readily be determined by one of ordinary skill in the art. The term "linker", identified where appropriate by the symbol X. X" or X", refers to a group or groups that covalently links from 2 to 10 ligands (as identified above) in a manner that provides for a compound capable of multivalency. Among other features, the linker is a ligand-orienting entity that permits attachment of multiple copies of a ligand (which may be the same or different) thereto. In some cases, the linker may itself be biologically active. The term "linker" does not, however, extend to cover solid inert supports such as beads, glass particles, fibers, and the like. But it is understood that the multibinding compounds of this invention can be attached to a solid support if desired. For example, such attachment to solid supports can be made for use in separation and purification processes and similar applications. The term "library" refers to at least 3, preferably from 10 2 to 10 9 and more preferably from 10 2 to 10 4 multimeric compounds. Preferably, these compounds are prepared as a multiplicity of compounds in a single solution or reaction mixture which permits facile synthesis thereof. In one embodiment, the library of multimeric compounds can be directly assayed for multibinding properties. In another embodiment, each member of the library of multimeric compounds is first isolated and, optionally, characterized. This member is then assayed for multibinding properties. The term "collection" refers to a set of multimeric compounds w hich are prepared either sequentially or concuπently (e.g., combinatorially). The collection comprises at least 2 members; preferably from 2 to 10 9 members and still more preferably from 10 to 10 4 members. The term ' multimenc compound" refers to compounds compnsing from 2 to 10 ligands covalently connected through at least one linker hich compounds may or may not possess multibinding properties (as defined herein) 1 he term "pseudohahde" refers to functional groups w hich react in displacement reactions in a manner similar to a halogen Such functional groups include, by way of example, mesyl, tosyl, azido and cvano groups The extent to which multivalent binding is realized depends upon the efficiency with which the linker or linkers that joins the ligands presents these ligands to the aπay of available ligand binding sites Bevond presenting these ligands for multivalent interactions with ligand binding sites, the linker or linkers spatially constrains these interactions to occur within dimensions defined by the linker or linkers Thus, the structural features of the linker (valency, geometry, orientation, size, flexibility, chemical composition, etc ) are features of multibinding agents that play an important role in determining their activities The linkers used in this invention are selected to allow multivalent binding of ligands to the ligand binding sites of bactenal nbosomal RNA and/or of one or more proteins involved in nbosomal protein synthesis in the bactenum , wherever such sites are located on the receptor stmcture The ligands are covalently attached to the linker or linkers using conventional chemical techniques providing for covalent linkage of the ligand to the linker or linkers Reaction chemistnes resulting in such linkages are well known in the art and involve the use of complementary functional groups on the linker and ligand Preferably, the complementary functional groups on the linker are selected relative to the functional groups available on the ligand for bonding or which can be introduced onto the ligand for bonding Again, such complementary functional groups are well known in the art For example, reaction between a carboxylic acid of either the linker or the ligand and a primary or secondary amine of the ligand or the linker in the presence of suitable, well-known activating agents results in formation of an amide bond covalently linking the ligand to the linker; reaction between an amine group of either the linker or the ligand and a sulfonyl halide of the ligand or the linker results in formation of a sulfonamide bond covalently linking the ligand to the linker; and reaction between an alcohol or phenol group of either the linker or the ligand and an alkyl or aryl halide of the ligand or the linker results in formation of an ether bond covalently linking the ligand to the linker. Table I below illustrates numerous complementary reactive groups and the resulting bonds formed by reaction therebetween. Table I Representative Complementary Binding Chemistries First Reactive Group Second Reactive Group Xinkage hydroxyl isocyanate urethane amine epoxide β-hydroxyamine sulfonyl halide amine sulfonamide carboxyl amine amide hydroxyl alkyl/aryl halide ether aldehyde amine/NaCNBH 4 amine ketone amine/NaCNBH 4 amine amine isocyanate urea The linker is attached to the ligand at a position that retains ligand domain- ligand binding site interaction and specifically which permits the ligand domain of the ligand to orient itself to bind to the ligand binding site. Such positions and synthetic protocols for linkage are well known in the art. The term linker embraces everything that is not considered to be part of the ligand. The relative oπentation in which the ligand domains are displayed deπves from the particular point or points of attachment of the ligands to the linker, and on the framework geometry The determination of where acceptable substitutions can be made on a ligand is typicallv based on prior know ledge of structure-activity relationships (SAR) of the ligand and/or congeners and/or stmctural information about hgand-receptor complexes (e g , X-ray cr stallography , NMR, and the like) Such positions and the synthetic methods for covalent attachment are well known in the art Following attachment to the selected linker (or attachment to a significant portion of the linker, for example 2-10 atoms of the linker), the univalent hnker-hgand conjugate may be tested for retention of activity in the relevant assay Suitable linkers and ligands are discussed more fully below At present, it is prefeπed that the multibinding agent is a biv alent compound, e g , two ligands which are covalently linked to linker X Methodology The linker, when covalently attached to multiple copies of the ligands provides a biocompatible, substantially non-immunogenic multibinding compound The biological acti ity of the multibinding compound is highly sensitive to the valency, geometry, composition, size, flexibility or ngidity, etc of the linker and, in turn, on the overall stmcture of the multibinding compound, as well as the presence or absence of anionic or cationic charge, the relative hydrophobicity/hydrophihcity of the linker, and the like on the linker Accordingly, the linker is preferably chosen to maximize the biological activity of the multibinding compound The linker may be chosen to enhance the biological activity of the molecule In general, the linker may be chosen from any organic molecule constmct that onents two or more ligands to their ligand binding sites to permit multivalency In this regard, the linker can be considered as a "framework" on which the ligands are aπanged in order to bring about the desired hgand- onentmg result, and thus produce a multibinding compound For example, different onentations can be achieved by including in the framework groups containing mono- or polycychc groups, including ary 1 and/or heteroaryl groups, or stmctures incorporating one or more carbon-carbon multiple bonds (alkenyl, alkenylene, alkynyl or alkynylene groups) Other groups can also include oligomers and polymers which are branched- or straight-chain species In prefeπed embodiments, ngidity is imparted by the presence of cyclic groups (e g aryl, heteroaryl, cycloalkyl, heterocyclic, etc ) In other prefeπed embodiments, the ring is a six or ten member nng In still further prefeπed embodiments, the πng is an aromatic ring such as, for example, phenyl or naphthyl Different hydrophobic/hydrophihc characteπstics of the linker as well as the presence or absence of charged moieties can readily be controlled by the skilled artisan For example, the hydrophobic nature of a linker denved from hexamethylene diamine (H 2 N(CH 2 ) 6 NH 2 ) or related polyamines can be modified to be substantially more hydrophilic by replacing the alkylene group with a poly(oxyalkylene) group such as found in the commercially available "Jeffamines" By controlling the hydrophihcity/hydrophobicity, the ability of the compounds to cross the blood/brain barπer can be controlled This can be important when one wishes to maximize or minimize CNS effects Examples of molecular stmctures in which the above bonding patterns could be employed as components of the linker are shown below The identification of an appropriate framework geometry and size for ligand domain presentation are important steps in the constmction of a multibinding compound with enhanced activity. Systematic spatial searching strategies can be used to aid in the identification of prefeπed frameworks through an iterative process. Numerous strategies are known to those skilled in the art of molecular design and can be used for preparing compounds of this invention. It is to be noted that core stmctures other than those shown here can be used for determining the optimal framework display orientation of the ligands. The process may require the use of multiple copies of the same central core stmcture or combinations of different types of display cores. The above-described process can be extended to trimers and compounds of higher valency. Assays of each of the individual compounds of a collection generated as described above will lead to a subset of compounds with the desired enhanced activities (e.g., potency, selectivity, etc.). The analysis of this subset using a technique such as Ensemble Molecular Dynamics will provide a framework orientation that favors the properties desired. A wide diversity of linkers is commercially available (see, e.g., Available Chemical Directory (ACD)). Many of the linkers that are suitable for use in this invention fall into this category. Other can be readily synthesized by methods well known in the art and/or are described below. Having selected a prefeπed framework geometry, the physical properties of the linker can be optimized by varying the chemical composition thereof. The composition of the linker can be varied in numerous ways to achieve the desired physical properties for the multibinding compound. It can therefore be seen that there is a plethora of possibilities for the composition of a linker. Examples of linkers include aliphatic moieties, aromatic moieties, steroidal moieties, peptides, and the like. Specific examples are peptides or polyamides, hydrocarbons, aromatic groups, ethers, lipids, cationic or anionic groups, or a combination thereof. Examples are given below, but it should be understood that various changes may be made and equivalents may be substituted without departing from the true spirit and scope of the invention. For example, properties of the linker can be modified by the addition or insertion of ancillary groups into or onto the linker, for example, to change the solubility of the multibinding compound (in water, fats, lipids, biological fluids, etc.), hydrophobicity, hydrophilicity, linker flexibility, antigenicity, stability, and the like. For example, the introduction of one or more poly(ethylene glycol) (PEG) groups onto or into the linker enhances the hydrophilicity and water solubility of the multibinding compound, increases both molecular weight and molecular size and, depending on the nature of the unPEGylated linker, may increase the in vivo retention time. Further PEG may decrease antigenicity and potentially enhances the overall rigidity of the linker. Ancillary groups which enhance the water solubility/hydrophilicity of the linker and, accordingly, the resulting multibinding compounds are useful in practicing this invention. Thus, it is within the scope of the present invention to use ancillary groups such as, for example, small repeating units of ethylene glycols, alcohols, polyols (e.g., glycerin, glycerol propoxylate, saccharides, including mono-, oligosaccharides, etc.), carboxylates (e.g., small repeating units of glutamic acid, acrylic acid, etc.), amines (e.g., tetraethylenepentamine), and the like) to enhance the water solubility and or hydrophilicity of the multibinding compounds of this invention. In prefeπed embodiments, the ancillary group used to improve water solubility/hydrophilicity will be a polyether . The incorporation of lipophilic ancillary groups within the stmcture of the linker to enhance the lipophilicity and/or hydrophobicity of the multibinding compounds described herein is also within the scope of this invention. Lipophilic groups useful with the linkers of this invention include, by way of example only, aryl and heteroaryl groups which, as above, may be either unsubstituted or substituted with other groups, but are at least substituted with a group which allows their covalent attachment to the linker. Other lipophilic groups useful with the linkers of this invention include fatty acid derivatives which do not form bilayers in aqueous medium until higher concentrations are reached. Also within the scope of this invention is the use of ancillary groups which result in the multibinding compound being incorporated or anchored into a vesicle or other membranous stmcture such as a liposome or a micelle. The term "lipid" refers to any fatty acid derivative that is capable of forming a bilayer or a micelle such that a hydrophobic portion of the lipid matenal onents toward the bilayer while a hydrophilic portion onents toward the aqueous phase Hydrophilic characteπstics denve from the presence of phosphato, carboxylic, sulfato, amino, sulfhydryl, nitro and other like groups well known in the art Hydrophobicity could be confeπed by the inclusion of groups that include, but are not limited to, long chain saturated and unsaturated aliphatic hydrocarbon groups of up to 20 carbon atoms and such groups substituted by one or more aryl, heteroaryl, cycloalkyl, and/or heterocyclic group(s) Prefeπed lipids are phosphoglyceπdes and sphingohpids, representative examples of which include phosphatidylcholine, phosphatidylethanolamme, phosphatidylsenne, phosphatidylinositol, phosphatidic acid, palmitoyleoyl phosphatidylcholine, lysophosphatidylchohne, lysophosphatidyl-ethanolamine, dipalmitoylphosphatidylchohne, dioleoylphosphatidylchohne, distearoyl-phosphatidylchohne or dilinoleoylphosphatidylcholine could be used Other compounds lacking phosphoms, such as sphingohpid and glycosphmgolipid families are also within the group designated as lipid Additionally, the amphipathic lipids described above may be mixed with other lipids including tnglycendes and sterols The flexibility of the linker can be manipulated by the inclusion of ancillary groups which are bulky and/or πgid The presence of bulky or πgid groups can hinder free rotation about bonds in the linker or bonds between the linker and the ancillary group(s) or bonds between the linker and the functional groups Rigid groups can include, for example, those groups whose conformational lability is restrained by the presence of nngs and/or multiple bonds withm the group, for example, aryl, heteroaryl, cycloalkyl, cycloalkenyl, and heterocyclic groups Other groups which can impart ngidity include polypeptide groups such as ohgo- or polyprohne chains Rigidity may also be imparted by internal hydrogen bonding or by hydrophobic collapse Bulky groups can include, for example, large atoms, ions (e.g., iodine, sulfur, metal ions, etc.) or groups containing large atoms, polycyclic groups, including aromatic groups, non-aromatic groups and stmctures incorporating one or more carbon-carbon multiple bonds (i.e., alkenes and alkynes). Bulky groups can also include oligomers and polymers which are branched- or straight-chain species. Species that are branched are expected to increase the rigidity of the stmcture more per unit molecular weight gain than are straight-chain species. In prefeπed embodiments, rigidity is imparted by the presence of cyclic groups (e.g., aryl, heteroaryl, cycloalkyl, heterocyclic, etc.). In other prefeπed embodiments, the linker comprises one or more six-membered rings. In still further prefeπed embodiments, the ring is an aryl group such as, for example, phenyl or naphthyl. Rigidity can also be imparted electrostatically. Thus, if the ancillary groups are either positively or negatively charged, the similarly charged ancillary groups will force the presenter linker into a configuration affording the maximum distance between each of the like charges. The energetic cost of bringing the like-charged groups closer to each other will tend to hold the linker in a configuration that maintains the separation between the like-charged ancillary groups. Further ancillary groups bearing opposite charges will tend to be attracted to their oppositely charged counterparts and potentially may enter into both inter- and intramolecular ionic bonds. This non-covalent mechanism will tend to hold the linker into a conformation which allows bonding between the oppositely charged groups. The addition of ancillary groups which are charged, or alternatively, bear a latent charge when deprotected, following addition to the linker, including deprotection of a carboxyl, hydroxyl, thiol or amino group by a change in pH, oxidation, reduction or other mechanisms known to those skilled in the art which result in removal of the protecting group, is within the scope of this invention. In view of the above, it is apparent that the appropriate selection of a linker group providing suitable orientation, restricted/unrestricted rotation, the desired degree of hydrophobicity/hydrophilicity, etc. is well within the skill of the art. Eliminating or reducing antigenicity of the multibinding compounds described herein is also within the scope of this invention. In certain cases, the antigenicity of a multibinding compound may be eliminated or reduced by use of groups such as, for example, poly(ethylene glycol). As explained above, the multibinding compounds described herein comprise 2-10 ligands attached to a linker that links the ligands in such a manner that they are presented to the enzyme for multivalent interactions with ligand binding sites thereon/therein. The linker spatially constrains these interactions to occur within dimensions defined by the linker. This and other factors increases the biological activity of the multibinding compound as compared to the same number of ligands made available in monobinding form. The compounds of this invention are preferably represented by the empirical formula (L) p (X) q where L, X, p and q are as defined above. This is intended to include the several ways in which the ligands can be linked together in order to achieve the objective of multivalency, and a more detailed explanation is described below. As noted previously, the linker may be considered as a framework to which ligands are attached. Thus, it should be recognized that the ligands can be attached at any suitable position on this framework, for example, at the termini of a linear chain or at any intermediate position. The simplest and most prefeπed multibinding compound is a bivalent compound which can be represented as L-X-L, where each L is independently a ligand which may be the same or different and each X is independently the linker. Examples of such bivalent compounds are provided in Figure 56 where each shaded circle represents a ligand. A trivalent compound could also be represented in a linear fashion, i.e., as a sequence of repeated units L-X-L-X-L, in which L is a ligand and is the same or different at each occuπence, as can X. However, a trimer can also be a radial multibinding compound comprising three ligands attached to a central core, and thus represented as (L) 3 X, where the linker X could include, for example, an aryl or cycloalkyl group. Illustrations of trivalent and tetravalent compounds of this invention are found in Figures 57 and 58, respectively, where again, the shaded circles represent ligands. Tetravalent compounds can be represented in a linear aπay, e.g., L-X-L-X-L-X-L in a branched array, e.g., L-X-L-X-L L (a branched constmct analogous to the isomers of butane - i-butyl, tso-butyl, sec- butyl, and t-butyl) or in a tetrahedral aπay, e.g., X / 'L where X and L are as defined herein. Alternatively, it could be represented as an alkyl, aryl or cycloalkyl derivative as above with four (4) ligands attached to the core linker. The same considerations apply to higher multibinding compounds of this invention containing 5-10 ligands, as illustrated in Figure 59. However, for multibinding agents attached to a central linker such as aryl or cycloalkyl, there is a self-evident constraint that there must be sufficient attachment sites on the linker to accommodate the number of ligands present; for example, a benzene ring could not directly accommodate more than 6 ligands, whereas a multi-ring linker (e.g., biphenyl) could accommodate a larger number of ligands. Certain of the above described compounds may alternatively be represented as cyclic chains of the form: X X and variants thereof. All of the above variations are intended to be within the scope of the invention defined by the formula (L) p (X) . With the foregoing in mind, a prefeπed linker may be represented by the following formula: -X a -Z-(Y a -Z) m -Y b -Z-X a - in which: m is an integer of from 0 to 20; X a at each separate occuπence is selected from the group consisting of -0-, -S-, -NR-, -C(O)-, -C(0)0-, -C(0)NR-, -C(S), -C(S)0-, -C(S)NR- or a covalent bond where R is as defined below; Z is at each separate occuπence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene. cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, or a covalent bond; Y a and Y b at each separate occuπence are selected from the group consisting of: -S-S- or a covalent bond; in which: n is 0, 1 or 2; and R, R' and R" at each separate occuπence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic. Additionally, the linker moiety can be optionally substituted at any atom therein by one or more alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic group. In one embodiment of this invention, the linker (i.e., X, X' or X") is selected those shown in Table II: Table II Representative Linkers Linker -HN-(CH 2 ) 2 -NH-C(O)-(CH 2 )-C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(O)-(CH 2 ) 2 -C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 ) 3 -C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 ) 4 -C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 ) 5 -C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 ) 6 -C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 ) 7 -C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 ) 8 -C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 ) 9 -C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(O)-(CH 2 ) 10 -C(O)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 )„-C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(O)-(CH 2 ) 12 -C(O)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(O)-Z-C(O)-NH-(CH 2 ) 2 -NH- where Z is 1,2-phenyl -HN-(CH 2 ) 2 -NH-C(O)-Z-C(O)-NH-(CH 2 ) 2 -NH- where Z is 1,3-phenyl -HN-(CH 2 ) 2 -NH-C(O)-Z-C(O)-NH-(CH 2 ) 2 -NΗ- where Z is 1,4-phenyl -HN-(CH 2 ) 2 -NH-C(O)-Z-O-Z-C(O)-NH-(CH 2 ) 2 -NH- where Z is 1,4-phenyl -HN-(CH,) ,-NH-C(O)-(CH 2 ) ,-CH(NH-C(0)-(CH 2 ) 8 -CH 3 )-C(0)-NH-(O ), NH- -HN-(CH 2 ) 2 -NH-C(O)-(CH 2 )-O-(CH 2 )-C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(O)-Z-C(O)-NH-(CH 2 ) 2 -NH- where Z is 5-(«-octadecyloxy)- 1,3-phenyl -HN-(CH 2 ) 2 -NH-C(O)-(CH 2 ) 2 -CH(NH-C(0)-Z)-C(O)-NH-(CH 2 ) 2 -NH- where Z is 4-biphenyl Linker -HN-(CH 2 ) 2 -NH-C(0)-Z-C(0)-NH-(CH 2 ) 2 -NH- where Z is 5-(n-butyloxy)- 1,3-phenyl -HN-(CH 2 ) 2 -NH-C(O)-(CH 2 ) g -trα/25-(CH=CH)-C(O)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(O)-(CH 2 ) ,-CH(NH-C(O)-(CH 2 ) P -CH 3 )-C(O)-NH-(CH 2 ),- H- -HN-(CH 2 ) 2 -NΗ-C(0)-(CH 2 ) 2 -CH(NH-C(0)-Z)-C(0)-NH-(CH 2 ) 2 -NH- where Z is 4-(n-octyl)-phenyl -HN-(CH 2 )-Z-O-(CH 2 ) 6 -0-Z-(CH 2 )-NH- where Z is 1 ,4-phenyl -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 ),-NH-C(0)-(CH 2 ) 3 -C(0)-NH-(CH,),-C(0)-NH- (CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 ) 2 -CH(NH-C(0)-Ph)-C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 )-N+((CH 2 ) 9 -CH 3 )(CH 2 -C(0)-NH-(CH 2 ) 7 -NH,)- (CH 2 )-C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-(CH 2 )-N((CH 2 ) 9 -CH 3 )-(CH 2 )-C(0)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NΗ-C(0)-(CH 2 ) ,-NH-C(0)-(CH 2 ) 2 -NH-C(0)-(CH,) 3 -C(0)-NH- (CH 2 ) 2 -C(0)-NH-(CH 2 ) 2 -C(d)-NH-(CH 2 ) 2 -NH- -HN-(CH 2 ) 2 -NH-C(0)-Z-C(0)-NH-(CH 2 ) 2 -NH- where Z is 5-hydroxy- 1,3-phenyl In another embodiment of this invention, the linker (i.e., X, X' or X") has the formula: wherein each R a is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene and arylene; each R b is independently selected from the group consisting of hydrogen, alkyl and substituted alkyl; and n ' is an integer ranging from 1 to about 20 In view of the above description of the linker, it is understood that the term "linker" when used in combination with the term "multibinding compound" includes both a covalently contiguous single linker (e g , L-X-L) and multiple covalently non-contiguous linkers (L-X-L-X-L) within the multibinding compound Ligands Any compound which binds to bactenal nbosomal RNA and/or to one or more proteins involved in πbosomal protein synthesis in the bacterium, and preferably, which inhibits protein expression through such binding, can be used as a ligand to prepare the compounds descnbed herein Such ligands are well known to those of skill in the art Preferably, each hgand, L, in the multibinding compound of formula I is independently selected from a compound of the formulas shown in Figure 1 The ligands shown in Figure 1 (and the precursors/synthons thereof) are well-known in the art and can be readily prepared using art-recognized starting matenals, reagents and reaction conditions By way of illustration, the following patents and publications disclose compounds, intermediates and procedures useful in the preparation of ligands with the formulas shown in Figure 1 or related compounds suitable for use in this invention Ahonkhai, V I et al., In Vitro Activity of U-57930E, a New Clindanncw Analog, Against Aerobic Gram-Positive Bacteria, Antimicrobial Agents and Chemotherapy. 21(6):902-905 (1982) Ballesta, J. P., et al., Peptidyltransferase inhibitors Structure-Activih Relationship Analvsis by Chemical Modification, Centra de Biologia Molecular, Chapter 44, pp 502-510, 199???. XAV PCT WO 95/07271 by Barbachyn, p 1-33 Barden, T. C, et al., In Vitro Antibacterial Activity of 9-(Glycylamιdo) tetracycline Derivatives, J. Med. Chem., 37(20):3205-321 1 (1995). Blackwood, R. K., et al., Some Transformations of Tetracycline at the 4- Position. Can. J. Chem, 43: 1382-1 88 H 65) Bnckner, S. J., et al, Synthesis and Antibacterial Activity of U-100592 and u- 100766, Two Oxazolidinone Antibacterial Agents for the Potential Treatment of Multidrug-Resistant Gram-Positive Bacterial Infections, J. Med. Chem, 39:673- 679 (1986). Cooperman, B.S. et al. Antibiotic Probes of Escherichia coli Ribosomal Peptidyltransf erase, Roche Institute of Molecular Biology, Chapter 42, pp 491- 501, 199???. XAV Cundliffe, Eric, Recognition Sites for Antibiotics within rRNA, Department of Biochemistry and Leicester Biocentre, LEI 7RH, UK, Chapter 41, pp 479-510, 199???.XAV Delaware, D. L, et al, Aminoglycoside Antibiotics (Dihydrostreptomycin Analogues), J. Antibiotics, XXXIX(2):251-258 (1986). Hemnton, P. M, et al. Oxidation and Alkylation of Spectinomycin Derivatives; Synthesis of Trospectomycin from Spectinomycin, J. Org. Chem, 678- 682 (1993). Kirst, Ph.D., H. A, 2 Semi-synthetic derivatives ofEiythromycin, Med. Chsn 30:57-88 (1993). LemieuX, R. U, et al. The Chemistry of Streptomycin, J. Am. Chem. Soc, 52:337-385 (1947). E. Merck Aktiengesellschaft, Tetracycline Derivatives, German Patent No.1,073,213, June, 1996 Mossa, J. S, et al. Streptomycin, Analytical Profiles of mg Substances, 16:507, 531-535,587 (1987). Rosenbrook, Jr., W, et al, Spectinomycin Modification, ACS Symposium, Series 125, 1980. Spahn, C. M. T, et al. Throwing a spanner in the works: antibiotics and the translation apparatus, Mol. Med, 74:423-430 (1996). Thomas, R. C, et al. Synthesis of Spectinomycin Analogs, ACS Symposium, Series 125, 121-130 (1980). Tohma, S, et al, Ashimycins A and B, new streptomycin Analogues, JL Antibiotics, XLII(8):1205-1212 (1989). Tucker, J. A, et al, Piperazinyl Oxazolidinone Antibacterial Agents Containing a pyridine, Diazene, or Triazene Heteroaromatic Ring, J. Med Chem, 41:3727-3735 (1988). White, D. R, et al. The Synthesis of Trospectomycin (6'-n- Propylspectinomycin, Il-63,366F) From Spp.rtinnmycin, Tetrahedron Letters, 30(12): 1469-1472 (1989). Each of these patents and publications is incorporated herein by reference in its entirety to the same extent as if each individual patent or publication was specifically and individually indicated to be incorporated by reference in its entirety. Dmgs such as chloramphenicol, erythromicin. clarithromycin, azithromycin, dirithromycin, flurithromycin clindamycin, lincomycin, quinopristin, dalfopristin, streptogramms, linezolid, U- 100480, U-101603, U-94901, U- 101244, pristinamycin, MJ-347-81F4A, HMR-3647, L-708299, A- 184656, L-708365, L- 701677, lexithromycin, RU-64004, CP-227182, CP-426027, TEA-0769, CP- 279107, RU-56006, RU-6652, RU-59616, L-744434, L-744433, L-740893, L- 709936, leucomycin, A- 179796, eperezolid, and U- 100480 inhibit ribosomal protein biosynthesis through binding to the 5 OS ribosomal subunit. They can be used to treat Bacterial infections, generally, and, more specifically, Pneumocystis carinii infections. Dmgs such as tetracycline, chlortetracycline, oxytetracycline, demeclocycline, methacycline, doxyeycline, minocycline, CL-331002, glycylcyclines, CL-331928, CL-344667, CL-329998 and PAM-MINO inhibit ribosomal protein biosynthesis through binding to the aminoacyl tRNA site on the 30S ribosomal unit. They can be used to treat bacterial infections, generally. Dmgs such as streptomycin, gentamicin, tobramycin, amikacin, netilimicin, kanamycin, neomycin, spectinomycin, dactimicin, paromomycin and trospectomycin inhibit ribosomal protein synthesis through binding to the 30S ribosomal unit. They can be used to treat bacterial infections, generally. Dmgs such as fusidic acid and purpuromycin inhibit protein synthesis through binding to soluble protein factors. They can be used to treat bacterial infections, generally. Preparation of Multibinding Compounds The multibinding compounds of this invention can be prepared from readily available starting materials using the following general methods and procedures. It will be appreciated that where typical or prefeπed process conditions (i.e., reaction temperatures, times, mole ratios of reactants, solvents, pressures, etc.) are given, other process conditions can also be used unless otherwise stated. Optimum reaction conditions may vary with the particular reactants or solvent used, but such conditions can be determined by one skilled in the art by routine optimization procedures. Additionally, as will be apparent to those skilled in the art, conventional protecting groups may be necessary to prevent certain functional groups from undergoing undesired reactions. The choice of a suitable protecting group for a particular functional group as well as suitable conditions for protection and deprotection are well known in the art. For example, numerous protecting groups, and their introduction and removal, are described in T. W. Greene and G. M. Wuts, Protecting Groups in Organic Synthesis, Second Edition, Wiley, New York, 1991 , and references cited therein. Any compound which binds to bacterial ribosomal RNA and/or to one or more proteins present in the bacterial ribosome, and, preferably, which inhibits or otherwise adversely affects protein expression, can be used as a ligand in this invention. As discussed in further detail below, numerous such compound are known in the art and any of these known compounds or derivatives thereof may be employed as ligands in this invention. Typically, a compound selected for use as a ligand will have at least one functional group, such as an amino, hydroxyl, thiol or carboxyl group and the like, which allows the compound to be readily coupled to the linker. Compounds having such functionality are either known in the art or can be prepared by routine modification of known compounds using conventional reagents and procedures. The patents and publications set forth above provide numerous examples of suitably functionalized macrolide antibiotics, aminoglycosides, lincosamides, oxazolidinones, streptogramins, tetracycline and other compounds which bind to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium, and intermediates thereof, which may be used as ligands in this invention. The ligands can be covalently attached to the linker through any available position on the ligands, provided that when the ligands are attached to the linker, at least one of the ligands retains its ability to bind to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium. Certain sites of attachment of the linker to the ligand are prefeπed based on known stmcture-activity relationships. Preferably, the linker is attached to a site on the ligand where stmcture-activity studies show that a wide variety of substituents are tolerated without loss of receptor activity. It will be understood by those skilled in the art that the following methods may be used to prepare other multibinding compounds of this invention. Ligand precursors, for example, ligands containing a leaving group or a nucleophilic group, can be covalently linked to a linker precursor containing a nucleophilic group or a leaving group, using conventional reagents and conditions. As shown in Scheme A (Figure 2), the reaction product of erythromyclamine and Fmoc protected glycinal followed by reduction of the resulting imine and deprotection (compound 103) can be reacted with a diacid under routine amidation conditions to afford a ligand dimer. As shown in Scheme B (Figure 3), the amine in erythromyclamine can be protected and a reactive hydroxy group reacted to form an imidazolide which can be reacted with a diamine to form a ligand dimer. As shown in Scheme C (Figure 4), an imidazolide can be reacted with an amino acid. The resulting compound has a carboxylic acid group which can be coupled with the free amine group in (103) using routine conditions. As shown in Scheme D (Figure 5), an imidazolide can be reacted with two equivalents of an amine to form a diurea compound. As shown in Scheme E (Figure 6), two equivalents of an amine-containing compound can be reacted with a diacid such as adipic acid ω form a di-amide. As shown in Scheme F (Figure 7), an imidazolide can be reacted with an amino acid to form a urea linkage, and the free carboxylic acid group from the amino acid can be coupled with an amine to form a ligand dimer. As shown in Scheme G (Figure 8) and Scheme H (Figure 9), two molecules containing amine groups can be reacted with a dibromide or a diacid to form the desired compound. As shown in Scheme I (Figure 10), two equivalents of a ligand containing an aldehyde group can be reacted with a linker containing two amine groups, and the resulting imine reduced to form a diamine. As shown in Scheme J (Figure 11 ), a ligand containing an amine group can be reacted with a linker containing an aldehyde group, and the resulting imine reduced to form a diamine. As shown in Scheme K (Figure 12), a ligand containing a secondary amine can be reacted with an Fmoc protected glycine and the resulting amine deprotected to form a primary amine derivative. Two equivalents of the primary amine can be reacted with a diacid to form a ligand dimer. As shown in Scheme L (Figure 13), a ligand with an aromatic amine group can be reacted to form an imidazolide Two equivalents of the imidazolide can be reactrd with a diamine to form a diurea compound As shown in Scheme M (Figure 14), the imidazolide from scheme L can be reacted with an ammo acid to form an amide linkage, and the free carboxylic acid group reacted with an amine on a second ligand to create a dimer with mixed ligands As shown in Scheme N (Figure 15), two equivalents of a ligand with an alpha-beta unsaturated ketone moiety can be reacted with a dithiol to form the desired product after the thiols add across the double bond on the ligands As shown in Scheme O (Figure 16), two equivalents of a ligand with a pπmary amme group can be reacted with a diacid under appropnate conditions to form a di-amide reaction product As shown in Scheme P (Figure 17), one equivalent of a ligand with an alpha-beta unsaturated ketone can be reacted with a linker including a thiol group and a carboxylic acid group such that the thiol adds across the double bond The free carboxylic acid is then free to react with an amme group on a second ligand to form a dimer As shown in Scheme Q (Figure 18), two equivalents of a ligand with an unsaturated ester linkage can also be reacted with a dithiol linker under conditions where the thiol groups add across the double bonds to form the desired product As shown in Scheme R (Figure 19), one equivalent of a first ligand containing an alpha-beta unsaturated ketone and one equivalent of a dithiol can be reacted such that the resulting product includes a reactive thiol group, which can then be reacted with a second ligand containing an unsaturated ester moiety, to form a mixed dimer. As shown in Scheme S (Figure 20), one equivalent of a ligand containing an unsaturated ester moiety can be reacted with one equivalent of a linker including a thiol and a carboxylic acid moiety to form an intermediate containing a free carboxylic acid group. This carboxylic acid group can then be reacted with a free amine group on a second ligand to form a mixed dimer. As shown in Scheme T (Figure 21), a ligand with more than one amine group can be reacted with a dihalide to form a mixture of dimers. As shown in Scheme U (Figure 22), a ligand with a primary amine group and one or more additional secondary amine groups can be selectively reacted with an aldehyde group on a second ligand to form a dimer without the need for an intermediate linker molecule. As shown in Scheme V (Figure 23), a ligand with a primary amine group and one or more additional secondary amine groups can be selectively reacted with a linker molecule containing two acid groups to form a dimer. As shown in Scheme W (Figure 24), a ligand with an unprotected amine group and one or more additional protected amine groups can be selectively reacted with a linker molecule with two bromo groups to form a dimer. As shown in Scheme X (Figure 24A), a ligand with an unprotected amine group and one or more additional protected amine groups can be selectively reacted with a linker molecule with a halide group and a carboxylic acid group to form an intermediate with a free carboxylic acid group, which can then be reacted with another ligand containing an amine group to form a mixed dimer. As shown in Scheme Y (Figure 25), one equivalent of a ligand with an amine group can be reacted with one equivalent of a linker with two acid groups to form an intermediate with a free carboxylic acid group. This intermediate can be reacted with a second ligand which includes an unprotected amine group and one or more additional protected amine groups to form a mixed dimer. As shown in Scheme Z (Figure 25A), a ligand with a secondary amine group can be reacted with a linker molecule containing a halide and a carboxylic acid group to form an intermediate with a free carboxylic acid group. The intermediate can then be reacted with a second ligand with a free amine group to form a mixed dimer. As shown in Scheme AA (Figure 26), one equivalent of a ligand containing an imidazolide group (and in Figure 26, a protected amine group) can be reacted with one equivalent of a linker molecule with two amine groups to form an intermediate with a free amine group. This intermediate can be reacted with a second ligand with an imidazolide group to form a mixed dimer (in Figure 26, the protected amine group was is then deprotected). As shown in Scheme BB (Figure 27), one equivalent of a ligand with a free primary amine group can be reacted with one equivalent of a diacid to form an intermediate with a free carboxylic acid group. This intermediate can be reacted with a second ligand with a free amine group to form a mixed dimer. As shown in Scheme CC (Figure 28), an intermediate ligand/dimer which includes a urethane group and a free carboxylic acid group can be reacted with a second ligand containing a free amine group to form mixed dimer. As shown in Scheme DD (Figure 29), one equivalent of a ligand with an imidazolide or other activated carboxylic acid group can be reacted with one equivalent of a linker with two amine groups to form an intermediate with a free amine group. This intermediate can be reacted with a second ligand with an imidazolide or other activated carboxylic acid group to form a mixed dimer. As shown in Scheme EE (Figure 30), one equivalent of a ligand with two free amine groups can be reacted with a linker with a halide and a carboxylic acid group to form a mixture of intermediates with a free carboxylic acid group. These intermediates can then be reacted with a second ligand with a free amine group to form a mixture of ligand dimers. As shown in Scheme FF (Figure 31), one equivalent of a ligand with an imidazolide or other activated carboxylic acid group can be reacted with one equivalent of a linker with two amine groups to form an intermediate with a free amine group, which can be reacted with a second ligand with an imidazolide or other activated carboxylic acid group to form a mixed dimer. As shown in Scheme GG (Figure 32), an intermediate formed by reacting a first ligand containing an amine group with a diacid can be reacted with a second ligand with a free amine group to form a mixed dimer. As shown in Scheme HH (Figure 33), an intermediate formed by reacting a first ligand containing an imidazolide group with a linker containing an amine group and a carboxylic acid can be reacted with a second ligand with a free amine group to form a mixed dimer. As shown in Scheme II (Figure 34), an intermediate formed by reacting a ligand containing an imidiazolide or other activated carboxylic acid group with a linker with two amine groups can be reacted with a second ligand with an imidiazolide or other activated carboxylic acid group to form a mixed dimer. As shown in Scheme JJ (Figure 35), a ligand with an amine group can be reacted with a linker with a halide and a carboxylic acid group to form an intermediate with a free halide group. This intermediate can be reacted with a second ligand with a free amine group to form a mixed dimer. As shown in Scheme KK (Figure 36), a ligand with an imidazolide or other active carboxylic acid group can be reacted with a linker with a primary amine group and a halide group to form an intermediate with a halide group. The halide group can be reacted with an amine on a second ligand to form a mixed dimer. As shown in Scheme LL (Figure 37), a ligand with a secondary amine group can be reacted with a linker with a halide group and a carboxylic acid group to form an intermediate with a free carboxylic acid group. This intermediate can be reacted with a second ligand with a free amine group to form a mixed dimer. As shown in Scheme MM (Figure 38), one equivalent of a ligand with a secondary amine group can be reacted with one equivalent of a dihalide linker to form an intermediate which has a halide group. This intermediate can be reacted with a second ligand with two free amino groups to form a mixture of mixed dimers. As shown in Scheme NN (Figure 39), one equivalent of a ligand with a secondary amine group can be reacted with a linker with a halide group and a carboxylic acid group to form an intermediate which has a free carboxylic acid group. This intermediate can be reacted with a second ligand with an amine group to form a mixed dimer. As shown in Scheme 00 (Figure 40), an intermediate formed from a ligand containing an amine group and a linker with two carboxylic acid groups can be reacted with a second ligand with an amine group to form a mixed dimer. As shown in Scheme PP (Figure 41), an intermediate formed by reacting a ligand containing an unsaturated ketone group with a linker with a thiol and a carboxyhc acid group can be reacted with one equivalent of a second ligand with an amine group to form a mixed dimer As shown in Scheme QQ (Figure 42), an intermediate formed by reacting a ligand containing an unsaturated ester group with a linker with a thiol and a carboxylic acid group can be reacted with one equivalent of a second ligand with an amme group to form a mixed dimer As shown in Scheme RR (Figure 43), one equivalent of an intermediate formed by reacting a ligand with a secondary amine group with a linker with a halide group and a carboxylic acid group can be reacted with a second ligand with an amme group to form a mixed dimer As shown in Scheme SS (Figure 44), a ligand with a pnmary amine group can be reacted with an intermediate formed by reacting a linker containing a thiol group and a carboxylic acid group with a hgand with an unsaturated ester group to form a mixed dimer As shown m Scheme TT (Figure 45), one equivalent of a ligand with an amme group can be reacted with one equivalent of a linker with two carboxylic acid groups to form an intermediate with a free carboxylic acid group, which can be reacted with a second ligand with an amine group to form a mixed dimer As shown in Scheme UU (Figure 46), an intermediate formed by reacting a ligand containing an imidazolide group with a linker molecule containing an amine group and a carboxylic acid group can be reacted with a second ligand with a free amine group to form a mixed dimer As shown m Scheme VV (Figure 47) and Scheme WW (Figure 48), an intermediate formed by reacting a ligand containing an unsaturated ester group with a linker containing a thiol and a carboxylic acid group can be reacted with a second ligand with an amine group to form a mixed dimer. As shown in Scheme XX (Figure 49), an intermediate formed by reacting a ligand containing an unprotected amine group (and, as shown in the figure, four protected amine groups) with a linker containing two halide groups can be reacted with a ligand containing an amine group to form a mixed dimer. The protected amine groups can then be deprotected. As shown in Scheme YY (Figure 50), a first ligand containing an unprotected amine group can be reacted with a dihalide linker to form an intermediate with a free halide group. This intermediate can be reacted with a ligand with two unprotected amine groups to form a mixture of mixed dimers. The protected amine groups can then be deprotected. As shown in Scheme ZZ (Figure 51), one equivalent of a ligand with an amine group can be reacted with one equivalent of a dihalide to form an intermediate with a free halide group. This intermediate can be reacted with a second ligand with two free amine groups to form a mixture of mixed dimers. As shown in Scheme AAA (Figure 52), two intermediates formed by reacting one equivalent of a ligand with two secondary amine groups with one equivalent of a linker with a halide and a carboxylic acid group are reacted with a second ligand containing a primary amine group to form a mixture of mixed dimers. As shown in Scheme BBB (Figure 53), one equivalent of a first ligand containing an amine group can be reacted with one equivalent of a linker molecule with two isocyanate groups to form an intermediate with a urea linkage and a free isocyanate group. This intermediate can be reacted with a second ligand with an amine group to form a mixed dimer with two urea linkages. As shown in Scheme CCC (Figure 54), a ligand with an amine group can be coupled with a linker with two carboxylic acid groups to form an intermediate with a free carboxylic acid group. This intermediate can be reacted with a second ligand with an amine group to form a mixed dimer. As shown in Scheme DDD (Figure 55), a ligand with an amine group can be reacted with a linker containing a halide group and a carboxylic acid group to form an intermediate with a free carboxylic acid group. This intermediate can be reacted with a second ligand with an amine group to form a mixed dimer. In each of the above reaction schemes, a particular antibiotic or combination thereof is listed. However, it is intended that these schemes are applicable to other ligands with similar reactive groups. Other methods are well known to those of skill in the art for coupling molecules such as the ligands described herein with the linker molecules described herein. For example, two equivalents of ligand precursor with a halide, tosylate, or other leaving group, can be readily coupled to a linker precursor containing two nucleophilic groups, for example, phenoxide groups, to form a dimer. The leaving group employed in this reaction may be any conventional leaving group including, by way of example, a halogen such as chloro, bromo or iodo, or a sulfonate group such as tosyl, mesyl and the like. When the nucleophilic group is a phenol, any base which effectively deprotonates the phenolic hydroxyl group may be used, including, by way of illustration, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, sodium hydroxide, potassium hydroxide, sodium ethoxide, triethylamine, diisopropylethylamine and the like. Nucleophilic substitution reactions are typically conducted in an inert diluent, such as tetrahydrofuran, NN-dimethylformamide, N,N-dimethylacetamide, acetone, 2- butanone, 1 -methyl-2-pyrrolidinone and the like. After the reaction is complete, the dimer is typically isolated using conventional procedures, such as extraction, filtration, chromatography and the like. By way of further illustration, dimers with a hydrophilic linker can be formed using a ligand precursor containing nucleophilic groups and a polyoxyethylene containing leaving groups, for example, poly(oxyethylene) dibromide (where the number of oxyethylene units is typically an integer from 1 to about 20) In this reaction, two molar equivalents of the ligand precursor are reacted with one molar equivalent of the poly(oxyethylene) dibromide in the presence of excess potassium carbonate to afford a dimer This reaction is typically conducted in N,N-dimethylformamide at a temperature ranging from about 25 °C to about 100 3 C for about 6 to about 48 hours Alternatively, the linker connecting the ligands may be prepared in several steps Specifically, a ligand precursor can first be coupled to an "adapter", l e , a bifunctional group having a leaving group at one end and another functional group at the other end which allows the adapter to be coupled to a intermediate linker group In some cases, the functional group used to couple to the intermediate linker is temporaπly masked with a protecting group ("PG") Representative examples of adapters include, by way of illustration, ter t-butyl bromoacetate, 1- Fmoc-2-bromoethylamme, l-tntyl-2-bromoethanethιol, 4-ιodobenzyl bromide, propargyl bromide and the like After the ligand precursor is coupled to the adapter and the protecting group is removed from the adapter's functional group (if a protecting group is present) to form an intermediate, two molar equivalents of the intermediate are then coupled with an intermediate linker to form a dimer Ligand precursors can be coupled wuh adapters which include both leaving groups and protecting groups to form protected intermediates The leaving group employed in this reaction may be any conventional leaving group including, by way of example, a halogen such as chloro, bromo or lodo, or a sulfonate group such as tosyl, mesyl and the like Similarly, any conventional protecting group may be employed including, by way of example, esters such as the methyl, tert- butyl, benzyl ("Bn") and 9-fluorenylmethyl ("Fm") esters Protected intermediates can then be deprotected using conventional procedures and reagents to afford deprotected intermediates. For example, tert- butyl esters are readily hydrolyzed with 95% trifluoroacetic acid in dichloromethane; methyl esters can be hydrolyzed with lithium hydroxide in tetrahydrofuran/water; benzyl esters can be removed by hydrogenolysis in the presence of a catalyst, such as palladium on carbon; and 9-fluorenylmethyl esters are readily cleaved using 20% piperidine in DMF. If desired, other well-known protecting groups and deprotecting procedures may be employed in these reactions to form deprotected intermediates. Similarly, ligand precursors having an adapter with an amine functional group can be prepared. Ligand precursors can be coupled with adapters which include leaving groups and protected amine groups to afford protected intermediates. The leaving group employed in this reaction may be any conventional leaving group. Similarly, any conventional amine protecting group may be employed including, by way of example, trityl, tert-butoxycarbonyl ("Boc"), benzyloxycarbonyl ("CBZ") and 9-fluorenylmethoxy-carbonyl ("Fmoc"). After coupling the adapter to the ligand precursor, the resulting protected intermediate is deprotected to afford a ligand precursor including an amine group using conventional procedures and reagents. For example, a trityl group is readily- removed using hydrogen chloride in acetone; a Boc group is removed using 95% trifluoroacetic acid in dichloromethane; a CBZ group can be removed by hydrogenolysis in the presence of a catalyst, such as palladium on carbon; and a 9- fluorenylmethoxycarbonyl group is readily cleaved using 20% piperidine in DMF to afford the deblocked amine. Other well-known amine protecting groups and deprotecting procedures may be employed in these reactions to form amine- containing intermediates and related compounds. Ligand precursors having an adapter, for example, one including a free carboxylic acid group or a free amine group, can be readily coupled to intermediate linkers having complementary functional groups to form multibinding compounds as described herein. For example, when one component includes a carboxylic acid group, and the other includes an amine group, the coupling reaction typically employs a conventional peptide coupling reagent and is conducted under conventional coupling reaction conditions, typically in the presence of a trialkylamine, such as ethyldiisopropylamine. Suitable coupling reagents for use in this reaction include, by way of example, carbodiimides, such as ethyl-3-(3- dimethylamino)propylcarbodiimide (EDC), dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) and the like, and other well-known coupling reagents, such as N,N'-carbonyldiimidazole, 2-ethoxy-l -ethoxycarbonyl- 1,2- dihydroquinoline (EEDQ), benzotriazol- 1 -yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP), O-(7-azabenzotriazol-l-yl)-N,N,N',N'- tetramethyluronium hexafluorophosphate (HATU) and the like. Optionally, well- known coupling promoters, such N-hydroxysuccinimide, 1-hydroxybenzotriazole (HOBT), l-hydroxy-7-azabenzotriazole (HOAT), N,N-dimethylaminopyridine (DMAP) and the like, may be employed in this reaction. Typically, this coupling reaction is conducted at a temperature ranging from about 0°C to about 60 °C for about 1 to about 72 hours in an inert diluent, such as THF, to afford the dimer. The multibinding compounds described herein can also be prepared using a wide variety of other synthetic reactions and reagents. For example, ligand precursors having aryliodide, carboxylic acid, amine and boronic acid functional groups can be prepared. Hydroxymethyl pyrrole can be readily coupled under Mitsunobu reaction conditions to various phenols to provide, after deprotection, functionalized intermediates. The Mitsunobu reaction is typically conducted by reacting hydroxymethyl pyπole and the appropriate phenol using diethyl azodicarboxylate (DEAD) and triphenylphosphine at ambient temperature for about 48 hours. Deprotection, if necessary, using conventional procedures and reagents then affords the functionalized intermediates. The functionalized intermediates can be employed in the synthesis of multibinding compounds. For example, aryliodide intermediates can be coupled with bis-boronic acid linkers to provide dimers. Typically, this reaction is conducted by contacting two molar equivalents of the aryliodide and one molar equivalent of the bis-boronic acid in the presence of tetrakis(triphenylphosphine)palladium(0). sodium carbonate and water in refluxing toluene. Aryliodide intermediates can also be coupled with acrylate intermediates or alkyne intermediate to afford dimers. These reactions are typically conducted by contacting two molar equivalents of aryliodide intermediates with one molar equivalent of either acrylates or alkynes in the presence of dichlorobis(triphenylphosphine)palladium (II), copper (I) iodide and diisopropylethylamine in N,N-dimethylformamide to afford the respective dimers. As will be readily apparent to those of ordinary skill in the art, the synthetic procedures described herein or those known in the art may be readily modified to afford a wide variety of compounds within the scope of this invention. Combinatorial Libraries The methods described herein lend themselves to combinatorial approaches for identifying multimeric compounds which possess multibinding properties. Specifically, factors such as the proper juxtaposition of the individual ligands of a multibinding compound with respect to the relevant array of binding sites on a target or targets is important in optimizing the interaction of the multibinding compound with its target(s) and to maximize the biological advantage through multivalency. One approach is to identify a library of candidate multibinding compounds with properties spanning the multibinding parameters that are relevant for a particular target. These parameters include: (1) the identity of ligand(s), (2) the orientation of ligands, (3) the valency of the constmct, (4) linker length, (5) linker geometry, (6) linker physical properties, and (7) linker chemical functional groups. Libraries of multimenc compounds potentially possessing multibinding properties (i.e., candidate multibinding compounds) and comprising a multiplicity of such variables are prepared and these libraries are then evaluated via conventional assays coπesponding to the ligand selected and the multibinding parameters desired. Considerations relevant to each of these variables are set forth below: Selection of Ligand(s) A single ligand or set of ligands is (are) selected for incorporation into the libraries of candidate multibinding compounds which library is directed against a particular biological target or targets, i.e, binding to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium, preferably in a manner which inhibits or otherwise adversely affects protein expression. The only requirement for the ligands chosen is that they are capable of interacting with the selected target(s). Thus, ligands may be known dmgs, modified forms of known drugs, substmctures of known dmgs or substrates of modified forms of known dmgs (which are competent to interact with the target), or other compounds. Ligands are preferably chosen based on known favorable properties that may be projected to be carried over to or amplified in multibinding forms. Favorable properties include demonstrated safety and efficacy in human patients, appropriate PK ADME profiles, synthetic accessibility, and desirable physical properties such as solubility, logP, etc. However, it is cmcial to note that ligands which display an unfavorable property from among the previous list may obtain a more favorable property through the process of multibinding compound formation; i.e, ligands should not necessarily be excluded on such a basis. For example, a ligand that is not sufficiently potent at a particular target so as to be efficacious in a human patient may become highly potent and efficacious when presented in multibinding form. A ligand that is potent and efficacious but not of utility because of a non-mechanism-related toxic side effect may have increased therapeutic index (increased potency relative to toxicity) as a multibinding compound. Compounds that exhibit short in vivo half-lives may have extended half-lives as multibinding compounds. Physical properties of ligands that limit their usefulness (e.g. poor bioavailability due to low solubility, hydrophobicity, hydrophilicity) may be rationally modulated in multibinding forms, providing compounds with physical properties consistent with the desired utility. Orientation: Selection of Ligand Attachment Points and Linking Chemistry Several points are chosen on each ligand at which to attach the ligand to the linker. The selected points on the ligand/linker for attachment are functionalized to contain complementary reactive functional groups. This permits probing the effects of presenting the ligands to their target binding site(s) in multiple relative orientations, an important multibinding design parameter. The only requirement for choosing attachment points is that attaching to at least one of these points does not abrogate activity of the ligand. Such points for attachment can be identified by stmctural information when available. For example, inspection of a co-crystal stmcture of a ligand bound to its target allows one to identify one or more sites where linker attachment will not preclude the ligand/target interaction. Alternatively, evaluation of ligand/target binding by nuclear magnetic resonance will permit the identification of sites non-essential for ligand/target binding. See, for example, Fesik, et al, U.S. Patent No. 5,891,643, the disclosure of which is incorporated herein by reference in its entirety. When such stmctural information is not available, utilization of stmcture-activity relationships (SAR) for ligands will suggest positions where substantial stmctural variations are and are not allowed. In the absence of both stmctural and SAR information, a library is merely selected with multiple points of attachment to allow presentation of the ligand in multiple distinct orientations. Subsequent evaluation of this library will indicate what positions are suitable for attachment. It is important to emphasize that positions of attachment that do abrogate the activity of the monomeric ligand may also be advantageously included in candidate multibinding compounds in the library provided that such compounds bear at least one ligand attached in a manner which does not abrogate intrinsic activity. This selection derives from, for example, heterobivalent interactions within the context of a single target molecule. For example, consider a ligand bound to its target, and then consider modifying this ligand by attaching to it a second copy of the same ligand with a linker which allows the second ligand to interact with the same target at sites proximal to the first binding site, which include elements of the target that are not part of the formal ligand binding site and or elements of the matrix suπounding the formal binding site, such as the membrane. Here, the most favorable orientation for interaction of the second ligand molecule may be achieved by attaching it to the linker at a position which abrogates activity of the ligand at the first binding site. Another way to consider this is that the SAR of individual ligands within the context of a multibinding stmcture is often different from the SAR of those same ligands in momomeric form. The foregoing discussion focused on bivalent interactions of dimeric compounds bearing two copies of the same ligand joined to a single linker through different attachment points, one of which may abrogate the binding/activity of the monomeric ligand. It should also be understood that bivalent advantage may also be attained with heteromeric constmcts bearing two different ligands that bind to common or different targets. Once the ligand attachment points have been chosen, one identifies the types of chemical linkages that are possible at those points. The most prefeπed types of chemical linkages are those that are compatible with the overall stmcture of the ligand (or protected forms of the ligand) readily and generally formed, stable and intrinsically innocuous under typical chemical and physiological conditions, and compatible with a large number of available linkers. Amide bonds, ethers, amines, carbamates, ureas, and sulfonamides are but a few examples of prefeπed linkages. Linker Selection In the library of linkers employed to generate the library of candidate multibinding compounds, the selection of linkers employed in this library of linkers takes into consideration the following factors: Valency: In most instances the library of linkers is initiated with divalent linkers. The choice of ligands and proper juxtaposition of two ligands relative to their binding sites permits such molecules to exhibit target binding affinities and specificities more than sufficient to confer biological advantage. Furthermore, divalent linkers or constmcts are also typically of modest size such that they retain the desirable biodistribution properties of small molecules. Linker Length: Linkers are chosen in a range of lengths to allow the spanning of a range of inter-ligand distances that encompass the distance preferable for a given divalent interaction. In some instances the prefeπed distance can be estimated rather precisely from high-resolution stmctural information of targets. In other instances where high-resolution stmctural information is not available, one can make use of simple models to estimate the maximum distance between binding sites either on adjacent receptors or at different locations on the same receptor. In situations where two binding sites are present on the same target (or target subunit for multisubunit targets), prefeπed linker distances are 2-20 A, with more prefeπed linker distances of 3-12 A. In situations where two binding sites reside on separate target sites, prefeπed linker distances are 20-100 A, with more prefeπed distances of 30-70 Λ. Linker Geometry and Rigidity: The combination of ligand attachment site, linker length, linker geometry, and linker rigidity determine the possible ways in which the ligands of candidate multibinding compounds may be displayed in three dimensions and thereby presented to their binding sites. Linker geometry and rigidity are nominally determined by chemical composition and bonding pattern, which may be controlled and are systematically varied as another spanning function in a multibinding aπay. For example, linker geometry is varied by attaching two ligands to the ortho, meta, and para positions of a benzene ring, or in cis- or trα/zs-aπangements at the 1,1- vs. 1,2- vs. 1,3- vs. 1,4- positions around a cyclohexane core or in cis- or trans-aπangements at a point of ethylene unsaturation. Linker rigidity is varied by controlling the number and relative energies of different conformational states possible for the linker. For example, a divalent compound bearing two ligands joined by 1,8-octyl linker has many more degrees of freedom, and is therefore less rigid than a compound in which the two ligands are attached to the 4,4' positions of a biphenyl linker. Linker Physical Properties: The physical properties of linkers are nominally determined by the chemical constitution and bonding patterns of the linker, and linker physical properties impact the overall physical properties of the candidate multibinding compounds in which they are included. A range of linker compositions is typically selected to provide a range of physical properties (hydrophobicity, hydrophilicity, amphiphilicity, polarization, acidity, and basicity) in the candidate multibinding compounds. The particular choice of linker physical properties is made within the context of the physical properties of the ligands they join and preferably the goal is to generate molecules with favorable PK/ADME properties. For example, linkers can be selected to avoid those that are too hydrophilic or too hydrophobic to be readily absorbed and/or distributed in vivo. Linker Chemical Functional Groups: Linker chemical functional groups are selected to be compatible with the chemistry chosen to connect linkers to the ligands and to impart the range of physical properties sufficient to span initial examination of this parameter. Combinatorial Synthesis Having chosen a set of n ligands (// being determined by the sum of the number of different attachment points for each ligand chosen) and m linkers by the process outlined above, a library of (n\)m candidate divalent multibinding compounds is prepared which spans the relevant multibinding design parameters for a particular target. For example, an aπay generated from two ligands, one which has two attachment points (Al , A2) and one which has three attachment points (Bl, B2, B3) joined in all possible combinations provide for at least 15 possible combinations of multibinding compounds: Al-Al A1-A2 Al-Bl A1-B2 A1-B3 A2-A2 A2-B1 A2-B2 A2-B3 Bl-Bl B1-B2 B1-B3 B2-B2 B2-B3 B3-B3 When each of these combinations is joined by 10 different linkers, a library of 150 candidate multibinding compounds results. Given the combmatoπal nature of the library, common chemistnes are preferably used to join the reactive functionalies on the ligands with complementary reactive functionalities on the linkers. The library therefore lends itself to efficient parallel synthetic methods. The combinatorial library can employ solid phase chemistries well known in the art wherein the ligand and/or linker is attached to a solid support. Alternatively and preferably, the combinatonal hbary is prepared in the solution phase After synthesis, candidate multibinding compounds are optionally purified before assaying for activity by, for example, chromatographic methods (e g, HPLC). Analysis of the Library Various methods are used to charactenze the properties and activities of the candidate multibinding compounds in the library to determine which compounds possess multibinding properties Physical constants such as solubility under vanous solvent conditions and logD/clogD values can be determined. A combination of NMR spectroscopy and computational methods is used to determine low-energy conformations of the candidate multibinding compounds in fluid media. The ability of the members of the library to bind to the desired target and other targets is determined by vanous standard methods, which include radioligand displacement assays for receptor and ion channel targets, and kinetic inhibition analysis for many enzyme targets. /// vitro efficacy, such as for receptor agonists and antagonists, ion channel blockers, and antimicrobial activity, can also be determined. Pharmacological data, including oral absorption, everted gut penetration, other pharmacokinetic parameters and efficacy data can be determined in appropriate models. In this way, key stmcture-activity relationships are obtained for multibinding design parameters which are then used to direct future work. The members of the library which exhibit multibinding properties, as defined herein, can be readily determined by conventional methods. First those members which exhibit multibinding properties are identified by conventional methods as described above including conventional assays (both in vitro and in vivo). Second, ascertaining the stmcture of those compounds which exhibit multibinding properties can be accomplished via art recognized procedures. For example, each member of the library can be encrypted or tagged with appropriate information allowing determination of the stmcture of relevant members at a later time. See, for example, Dower, et al. International Patent Application Publication No. WO 93/06121 ; Brenner, et al, Proc. Natl. Acad. Sci, USA, 89:5181 (1992); Gallop, et al, U.S. Patent No. 5,846,839; each of which are incorporated herein by reference in its entirety. Alternatively, the stmcture of relevant multivalent compounds can also be determined from soluble and untagged libaries of candidate multivalent compounds by methods known in the art such as those described by Hindsgaul, et al, Canadian Patent Application No. 2,240,325 which was published on July 11, 1998. Such methods couple frontal affinity chromatography with mass spectroscopy to determine both the stmcture and relative binding affinities of candidate multibinding compounds to receptors. The process set forth above for dimenc candidate multibinding compounds can, of course, be extended to tnmenc candidate compounds and higher analogs thereof Follow-up Synthesis and Analysis of Additional Libranes Based on the information obtained through analysis of the initial library, an optional component of the process is to ascertain one or more promising multibinding "lead" compounds as defined by particular relative ligand onentations, linker lengths, linker geometπes, etc Additional libranes can then be generated around these leads to provide for further information regarding stmcture to activity relationships These aπays typically bear more focused vaπations in linker stmcture in an effort to further optimize target affinity and/or activity at the target (antagonism, partial agonism, etc ). and/or alter physical properties By iterative redesign/analysis using the novel pπnciples of multibinding design along with classical medicinal chemistry, biochemistry, and pharmacology approaches, one is able to prepare and identify optimal multibinding compounds that exhibit biological advantages towards their targets and as therapeutic agents To further elaborate upon this procedure, suitable divalent linkers include, by way of example only, those denved from dicarboxylic acids, disulfonylhalides, dialdehydes, diketones, dihahdes, diisocyanates, diammes, diols, mixtures of carboxylic acids, sulfonylhalides, aldehydes, ketones, halides, isocyanates, amines and diols In each case, the carboxylic acid, sulfonylhalide, aldehyde, ketone, halide, isocyanate, amine and diol functional group is reacted with a complementary functionality on the hgand to form a covalent linkage Such complementary functionality is well known in the art as illustrated in the following table Representative Complementary Binding Chemisties First Reactive Group Second Reactive Group I-inkage hydroxyl isocyanate urethane amine epoxide β-hydroxyamine sulfonyl halide amine sulfonamide carboxyl acid amine amide hydroxyl alkyl/aryl halide ether aldehyde amine(+ reducing agent) amine ketone amine(+ reducing agent) amine amine isocyanate urea Exemplary linkers include the following linkers identified as X-1 through s set forth below: -β1- Pharmaceutical Formulations When employed as pharmaceuticals, the compounds of this invention are usually administered in the form of pharmaceutical compositions. These compounds can be administered by a variety of routes including oral, rectal, transdermal. subcutaneous, intravenous, intramuscular, and intranasal. These compounds are effective as both injectable and oral compositions. Such compositions are prepared in a manner well known in the pharmaceutical art and comprise at least one active compound. This invention also includes pharmaceutical compositions which contain, as the active ingredient, one or more of the compounds described herein associated with pharmaceutically acceptable earners. In making the compositions of this invention, the active ingredient is usually mixed with an excipient, diluted by an excipient or enclosed within such a carrier which can be in the form of a capsule, sachet, paper or other container. When the excipient serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, symps, aerosols (as a solid or in a liquid medium), ointments containing, for example, up to 10% by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions, and sterile packaged powders. In preparing a formulation, it may be necessary to mill the active compound to provide the appropriate particle size prior to combining with the other ingredients. If the active compound is substantially insoluble, it ordinarily is milled to a particle size of less than 200 mesh. If the active compound is substantially water soluble, the particle size is normally adjusted by milling to provide a substantially uniform distribution in the formulation, e.g, about 40 mesh. Some examples of suitable excipients include lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyv lny pyπohdone, cellulose, sterile water, syrup, and methy l cellulose The formulations can additionally include lubncatmg agents such as talc, magnesium stearate. and mineral oil etting agents, emulsifying and suspending agents, preserving agents such as methy 1- and propylhydroxv-benzoates, sweetening agents, and fla oπng agents The compositions of the invention can be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient by employing procedures known in the art The compositions are preferably formulated in a unit dosage form, each dosage containing from about 0 001 to about 1 g. more usually about 1 to about 30 mg, of the active ingredient The term "unit dosage forms" refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active matenal calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient Preferably, the compound of formula I above is employed at no more than about 20 weight percent of the pharmaceutical composition, more preferably no more than about 15 weight percent, with the balance being pharmaceutically inert carner(s) The active compound is effective over a wide dosage range and is generally administered in a pharmaceutically effective amount. It. will be understood, however, that the amount of the compound actually administered will be determined by a physician, in the light of the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered and its relative activity, the age, weight, and response of the individual patient, the seventy of the patient's symptoms, and the like For prepanng solid compositions such as tablets, the pnncipal active ingredient is mixed with a pharmaceutical excipient to form a solid preformulation composition containing a homogeneous mixture of a compound of the present mvention When refernng to these preformulation compositions as homogeneous, it is meant that the activ e ingredient is dispersed ev enly throughout the composition so that the composition may be readily subdivided into equallv effectiv e unit dosage forms such as tablets, pills and capsules This solid prelormulation is then subdivided into unit dosage forms of the type descnbed abo e containing from, for example, 0 1 to about 500 mg of the activ e ingredient of the present inv ention The tablets or pills of the present invention may be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action For example, the tablet or pill can compnse an inner dosage and an outer dosage component, the latter being in the form of an envelope ov er the former The two components can be separated bv an enteπc layer which sen es to resist disintegration m the stomach and permit the inner component to pass intact into the duodenum or to be delayed in release A vanety of mateπals can be used for such entenc layers or coatings, such mateπals including a number of polymeπc acids and mixtures of polymeπc acids with such matenals as shellac, cetyl alcohol, and cellulose acetate The liquid forms m which the novel compositions of the present invention may be incorporated for administration orally or by injection include aqueous solutions, suitably flavored symps, aqueous or oil suspensions, and flavored emulsions with edible oils such as com oil, cottonseed oil, sesame oil, coconut oil, or peanut oil, as well as elixirs and similar pharmaceutical vehicles Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders The liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as descnbed supi a Preferably the compositions are administered by the oral or nasal respiratory route for local or systemic effect Compositions in preferably pharmaceutically acceptable solvents may be nebulized by use of inert gases Nebulized solutions may be inhaled directly from the nebulizing device or the nebulizing dev ice may be attached to a face mask tent, or intermittent positive pressure breathing machine Solution, suspension, or powder compositions may be administered, preferably orally or nasally, from devices which deliver the formulation in an appropriate manner The following formulation examples illustrate representative pharmaceutical compositions of the present invention. Formulation Example 1 Flard gelatin capsules containing the following ingredients are prepared Quantity Ingredient img, capsule) Active Ingredient 30.0 Starch 305.0 Magnesium stearate 5.0 The above ingredients are mixed and filled into hard gelatin capsules in 340 mg quantities Formulation Example 2 A tablet foπnula is prepared using the ingredients below * Quantity Ingredient (mg/tablet 1 ! Active Ingredient 25.0 Cellulose, microcrystalline 200.0 Colloidal silicon dioxide 10.0 Steaπc acid 5.0 The components are blended and compressed to form tablets, each eighing 240 mg Formulation Example 3 A dry powder inhaler formulation is prepared containing the following components Ingredient Weight ° „ Active Ingredient 5 Lactose 95 The active ingredient is mixed ith the lactose and the mixture is added to a dry powder inhaling appliance Formulation Example 4 Tablets, each containing 30 mg of active ingredie- \ are prepared as follows Quantity Ingredient (me/tablet) Active Ingredient 30 0 mg Starch 45 0 mg Microcrystalline cellulose 35.0 mg Polyvinylpyrrolidone (as 10%) solution in steπle water) 4.0 mg Sodium carboxymethyl starch 4 5 mg Magnesium stearate 0 5 mg Talc 1 .0 mg Total 120 mg The active ingredient, starch and cellulose are passed through a No. 20 mesh U.S. sieve and mixed thoroughly The solution of polyvinylpyrrolidone is mixed with the resultant powders, which are then passed through a 16 mesh U.S sieve The granules so produced are dπed at 50 c to 60°C and passed through a 16 mesh U.S. sieve. The sodium carboxymethyl starch, magnesium stearate, and talc, previously passed through a No 30 mesh U S. sieve, are then added to the g ranules which, after mixing, are compressed on a tablet machine to yield tablets each weighing 120 mg. Formulation Example 5 Capsules, each containing 40 mg of medicament are made as follows Quantity Ingredient ( mg capsule) Activ e Ingredient 40 0 mg Starch 109 O mg Magnesium stearate 1 .0 g Total 150 O mg The activ e ingredient, starch, and magnesium stearate are blended, passed through a No 20 mesh U S siev e, and filled into hard gelatin capsules in 150 mg quantities Formulation Example 6 Suppositones. each containing 25 mg of activ e ingredient are made as follows Ingredient Amount Active Ingredient 25 mg Saturated fatty acid glycerides to 2,000 mg The active ingredient is passed through a No 60 mesh U S sieve and suspended in the saturated fatty acid glyceπdes previously melted using the minimum heat necessary The mixture is then poured into a suppository mold of nominal 2 0 g capacity and allowed to cool Formulation Example 7 Suspensions, each containing 50 mg of medicament per 5 0 mL dose are made as follows Ingredient Amount Active Ingredient 50 O mg Xanthan gum 4 O mg Sodium carboxymethyl cellulose ( 11%) Microcrystalline cellulose (89%) 50 O mg Sucrose 1 75 g Sodium benzoate l O O mg Flavor and Color q v Punfied water to 5 0 mL The active ingredient, sucrose and xanthan gum are blended, passed through a No 10 mesh U.S. sieve, and then mixed with a previously made solution of the microcrystalline cellulose and sodium carboxymethyl cellulose in water The sodium benzoate. flav or, and color are diluted w ith some of the water and added w ith stirnng Sufficient water is then added to produce the required olume Formulation Example 8 A formulation may be prepared as follo s Quantity Ingredient (mg, capsule) Active Ingredient 15 O mg Starch 407 0 mg Magnesium stearate 3.0 g Total 425 0 mg The activ e ingredient, starch, and magnesium stearate are blended, passed through a No 20 mesh U S sieve, and filled into hard gelatin capsules in 425 0 mg quantities Eormulation Example 9 A formulation may be prepared as follows Ingredient Quantity Active Ingredient 5 O mg Formulation Example 10 A topical formulation may be prepared as follows Ingredient Quantity Active Ingredient 1-lO g Emulsifying Wax 30 g Liquid Paraffin 20 g White Soft Paraffin to 100 g The white soft paraffin is heated until molten The liquid paraffin and emulsifying wax are incorporated and stiπed until dissolved The active ingredient is added and stirnng is continued until dispersed The mixture is then cooled until solid Another prefeπed formulation employed in the methods of the present inv ention employs transdermal dehverv devices ("patches ) Such transdermal patches may be used to prov ide continuous or discontinuous infusion of the compounds of the present inv ention in controlled amounts The constmction and use of transdermal patches for the delivery of pharmaceutical agents is well known in the art See, e g . U S Patent 5.023,252, issued June 1 1. 1991 , herein incorporated by reference in its entirety Such patches may be constmcted for continuous, pulsatile, or on demand delivery of pharmaceutical agents Other suitable formulations for use in the present inv ention can be found in Remington's Pharmaceutical Sciences Mace Publishing Company , Philadelphia. PA. 17th ed (1985) Utility The multibinding compounds of this invention are macrolide antibiotics, aminoglycosides, Imcosamides. oxazohdmones, streptogramms, tetracycline or other compounds which are known to bind bactenal πbosomal RNA and/or one or more proteins involved in nbosomal protein synthesis in the bactenum Accordingly, the multibinding compounds and pharmaceutical compositions of this invention are useful m the treatment and prevention of bactenal infections Examples of bactenal infections which can be treated using the compounds descnbed herein include gram positive, gram negative and anaerobic bactenal infections When used in treating or ameliorating such conditions, the compounds of this invention are typically delivered to a patient in need of such treatment by a pharmaceutical composition compnsing a pharmaceutically acceptable diluent and an effective amount of at least one compound of this invention The amount of compound administered to the patient will vary depending upon what compound and/or composition is being administered, the purpose of the administration, such as prophy laxis or therapy , the state of the patient the manner of administration, and the like In therapeutic applications, compositions are administered to patient already suffenng from a bactenal infection Amounts effectiv e for this use w ill depend on the judgment of the attending clinician depending upon factors such as the degree or seventy of the disorder in the patient, the age. w eight and general condition of the patient, and the like The pharmaceutical compositions of this invention mav contain more than one compound of the present inv ention As noted above, the compounds administered to a patient are in the form of pharmaceutical compositions descnbed abov e which can be administered by a vanety of routes including oral, rectal, transdermal, subcutaneous, intravenous, intramuscular, etc These compounds are effectiv e as both injectable and oral deliverable pharmaceutical compositions Such compositions are prepared in a manner well known in the pharmaceutical art and comprise at least one active compound The multibinding compounds of this invention can also be administered in the form of pro-dmgs. I e , as denvatives which are converted into a biologicalh active compound in vivo Such pro-dmgs will typically include compounds in which, for example, a carboxylic acid group, a hydroxyl group or a thiol group is converted to a biologically liable group, such as an ester, lactone or thioester group which will hydrolyze in vivo to reinstate the respective group The compounds can be assayed to identifv which of the multimenc ligand compounds possess multibinding properties First, one identifies a ligand or mixture of ligands which each contain at least one reactive functionality and a library of linkers which each include at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand Next one prepares a multimenc ligand compound library by combining at least two stoichiometπc equiv alents of the ligand or mixture of ligands w ith the library of linkers under conditions wherein the complementary functional groups react to form a covalent linkage between the linker and at least tw o of the ligands The multimenc ligand compounds produced in the library can be assayed to identify multimenc ligand compounds which possess multibinding properties The method can also be performed using a library of ligands and a linker or mixture of linkers The preparation of the multimenc ligand compound library can be achieved by either the sequential or concuπent combination of the two or more stoichiometnc equivalents of the ligands with the linkers The multimenc ligand compounds can be dimenc, for example, homodimenc or heteromeric A heteromenc ligand compound library can be prepared by sequentially adding a first and second ligand. Each member of the multimenc ligand compound library can be isolated from the library, for example, by preparative liquid chromatography mass spectrometry (LCMS) The linker or linkers can be flexible linkers, ngid linkers, hydrophobic linkers, hydrophilic linkers, linkers of different geometry, acidic linkers, basic linkers, linkers of different polaπzabihty and/or polaπzation or amphiphihc linkers. The linkers can include linkers of different chain lengths and/or which have different complementary reactive groups In one embodiment, the linkers are selected to have different linker lengths ranging from about 2 to 100A. The ligand or mixture of ligands can have reactive functionality at different sites on the ligands. The reactive functionality can be, for example, carboxylic acids, carboxylic acid halides, carboxyl esters, ammes, halides, pseudohalides. isocyanates, vinyl unsaturation. ketones, aldehydes, thiols, alcohols, anhydndes. boronates, and precursors thereof, as long as the reactive functionality on the ligand is complementary to at least one of the reactive groups on the linker so that a covalent linkage can be formed between the linker and the hgand A library of multimenc ligand compounds can thus be formed which possesses multiv alent properties Multimenc ligand compounds possessing multibinding properties can be identified in an iterative method by prepanng a first collection or iteration of multimenc compounds by contacting at least t o stoichiometπc equivalents of the ligand or mixture of ligands which target bactenal nbosomal RNA and/or one or more proteins involved in nbosomal protein synthesis in the bactenum with a linker or mixture of linkers, where the ligand or mixture of ligands includes at least one reactive functionality and the linker or mixture of linkers includes at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand The hgand(s) and hnker(s) are reacted under conditions which form a covalent linkage between the linker and at least two of the ligands. The first collection or iteration of multimenc compounds can be assayed to assess which if any of the compounds possess multibinding properties The process can be repeated until at least one multimenc compound is found to possess multibinding properties By evaluating the particular molecular constraints which are imparted or are consistent with imparting multibinding properties to the multimenc compound or compounds in the first iteration, a second collection or iteration of multimenc compounds which elaborates upon the particular molecular constraints can be assayed, and the steps optionally repeated to further elaborate upon said molecular constraints For example, the steps can be repeated from between 2 and 50 times, more preferably, between 5 and 50 times The following synthetic and biological examples are offered to illustrate this invention and are not to be constmed in any way as limiting the scope of this invention. Unless otherwise stated, all temperatures are in degrees Celsius EXAMPLES In the examples below, the following abbreviations have the following meanings. If an abbreviation is not defined, it has its generally accepted meaning A Angstroms cm centimeter DCC dicy clohexyi carbodnmide DMF NN-dimethylformamide DMSO dimethyisulfoxide EDTA ethylenediaminetetraacetic acid g gram HPLC high performance liquid chromatography MEM minimal essential medium mg milligram MIC minimum inhibitory concentration min minute mL millihter mm millimeter mmol milhmol N normal THF tetrahydrofuran μL microhters μm microns ANALYTICAL EXAMPLES Example 1 : Binding Test Methods for performing affinity labeling studies, for example, with chloramphenicol, are known to those of skill in the art. See, for example, Cooperman, "Functional sites on the E. coli ribosome as defined by affinity labeling," p. 531-554 (1980), Chambhss et al, in Ribosomes- Stmcture. Function and Genetics. University Park Press, Baltimore; Cooperman, Affinity labeling of ribosomes, Methods Enzymol.. 164:341-361 (1988); and Jaynes et al. Biochemistry, 17:561-569 (1978). Such methods can be used to determine the binding of the compounds of the present invention to various positions on ribosomal RNA and/or to proteins involved in bacterial protein synthesis. BIOLOGICAL EXAMPLES Example 1 Determination of Antibacterial Activity /// Vitro Determination of Antibacterial Activity Bacteria are obtained and phenotyped based on their sensitivity to different antibiotics including those that interfere with ribosomal protein synthesis. Minimal mhibitory concentrations ( MICs) are measured in a microdilution broth procedure under NCCLS guidelines The compounds are senally diluted into Mueller- Hinton broth in 96-w ell microtiter plates Overnight cultures of bactenal strains are diluted based on absorbance at 600 nm so that the final concentration in each well was 5 x 10' cfu/ml Plates are returned to a 35°C incubator The following day (or 24 hours in the case of Enterococci strains), MICs are determined by isual inspection of the plates Bacterial strains which may be tested in this model include, but are not limited to, those described herein Growth conditions may be modified as necessary for each particular strain Growing conditions and grow th media for the strains descnbed herein are known in the art Determination of Kill Time Expeπments to determine the time required to kill the bactena are conducted These expeπments are conducted with both staphylococcus and enterococcus strains. Bπefly, several colonies are selected from an agar plate and grown at 35°C under constant agitation until a turbidity of approximately 1.5 X 10 8 CFU/ml is achieved The sample is diluted to about 6 x 10" CFU/ml and incubated at 35°C under constant agitation. At vanous times, aliquots are removed and five ten-fold senal dilutions are performed The pour plate method is used to determine the number of colony forming units (CFUs). /// Vivn Determination of Antibactenal Activity Acute tolerabihty studies in mice In these studies, the compounds to be evaluated are administered either intravenously or subcutaneously and observed for 5- 15 minutes If there are no adverse effects, the dose is increased in a second group of mice This dose incrementation continues until mortality occurs, or the dose is maximized. Generally . dosing begins at 20 mg/kg and increases by 20 mg kg each time until the maximum tolerated dose (MTD) is achieved Bioav ailability studies in mice Mice are administered the compound to be ev aluated either intravenouslv or subcutaneously at a therapeutic dose (in general, approximately 50 mg/kg) Groups of animals are placed in metabolic cages so that uπne and feces may be collected for analysis Groups of animals (n-3) are sacnficed at vanous times (10 min. 1 hour and 4 hours) Blood is collected by cardiac puncture and the follow ing organs are harvested lung, liver, heart, brain, kidney, and spleen Tissues were eighed and prepared for HPLC analysis HPLC analysis on the tissue homogenates and fluids is used to determine the concentration of the compound Metabolic products resulting from changes to the compound are also determined Mouse septecemia model In this model, an appropπately v imlent strain of bacteπa (most commonly S aureus, or E faecahs or E faecium) is administered lntrapeπtoneally to mice (N=5 to 10 mice per group) The bacteπa was combined with hog gastnc mucin to enhance virulence The dose of bacteπa (normally 10 s - 10 ) is that which is sufficient to induce mortality in all of the mice over a three day penod One hour after the bacteria is administered, the compound to be evaluated is administered in a single dose, either IV or subcutaneously Each dose is administered to groups of 5 to 10 mice, at doses that typically range from a maximum of about 20 mg/kg to a minimum of less than 1 mg/kg A positive control (normally β-lactam with β- lactam sensitive strains) is administered in each expeπment The dose at which approximately 50% of the animals are saved is calculated from the results Neutropemc thigh model In this model, antibactenal activity of the compound to be evaluated is evaluated against an appropπately vimlent strain of bacteπa (most commonly S aureus) Mice are initially rendered neutropemc by administration of cyclophosphamide at 200 ma kg on day 0 and day 2. On day 4. they are infected in the left antenor thigh by an IM injection of a single dose of bacteria The mice are administered the compound one hour after the administration of bacteria. At vanous later times (normally 1 , 2.5. 4 and 24 hours) the mice are sacrificed (3 per time point). The thigh is excised, homogenized and the number of CFUs (colony forming units) is determined by plating. Blood is also plated to determine the CFUs in the blood. Pharmacokinetic studies The rate at which the compound to be evaluated is remov ed from the blood can be determined in either rats or mice. In rats, the test animals are cannulated in the jugular vein. A compound is administered via tail vein injection, and at various time points (normally 5, 15, 30, 60 minutes and 2, 4, 6 and 24 hours) blood is withdrawn from the cannula. In mice, a compound is also administered via tail vein injection, and at various time points. Blood is normally obtained by cardiac puncture. The concentration of the remaining compound is determined by HPLC. PREPARATIVE EXAMPLES Example 1 : Preparation of (113), a compound of Formula I via Scheme A Erythromyclamine (100) (10 mmol) is slurried in methanohanhydrous dimethylformamide, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (20 mmol) and Fmoc glycinal (101) (10 mmol) (prepared as described by Salvi et al. Tetrahedron Lett. 1994, 35, 1181-1 184). After 2 hours the reaction mixture is cooled in an ice water bath and treated further with sodium cyanoborohydride (4.0 mmol) and trifluoroacetic acid (30 mmol). After 2 additional hours the cmde product is concentrated under reduced pressure and fractionated by reverse-phase HPLC to afford the desired product (102). The above product (102) is then dissolved in anhydrous dimethylformamide (10 mL), stirred at room temperature and treated with excess piperidine (1.0 mL). After one hour the cmde products are concentrated under reduced pressure and fractionated by rev erse-phase HPLC to afford the desired product (103). Succinic acid (104) (2 0 mmol) is dissolv ed in 10 mL anhydrous dimethylformamide and treated sequentially w ith hvdroxybenzotnazole (5 0 mmol). diisopropylethyl amine (4 0 mmol) and PvBOP (4 0 mmol) After stirnng for 15 minutes at room temperature, the activated diacid is treated with compound (103) (4 0 mmol) and the coupling reaction mixture is stiπed ov ernight at room temperature Volatiles are removed under v acuum and the cmde is fractionated bv reverse-phase HPLC to afford the title product after lvophohzation of the appropπate fractions The chemistry is detailed below in the following reaction scheme Example 2: Preparation of (108). a compound of Formula II via Scheme B. Erythromyclamine (100) (34.0 mmol) is dissolved in THF under a nitrogen atmosphere. Di-tert-buty dicarbonate (Boc-,0) (68.0 mmol) dissolved in dichloromethane is added dropwise to the stiπed solution. The course of the reaction is followed by TLC and stirring is continued at room temperature until the reaction is judged complete. The reaction mixture is evaporated giving a precipitate that is collected by filtration. The precipitate is πnsed with ether to afford the desired product, which is treated with acetic anhydride in dichloromethane and purified by silica gel chromatography. The product (10 mmol) is then dissolved in toluene, stiπed in an ice/water bath, and treated sequentially with K : C0 3 (100 mmol) and carbonyldiimidazole (10 mmol). The ice bath is removed and the reaction mixture is allowed to warm to room temperature. The imidazolide (105) thus produced is used without further manipulation in the coupling reactions described below. 1 ,4-Diaminobutane (106) (2.0 mmol) is dissolved in toluene/DMF, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (4.0 mmol) and imidazolide (105) (4.0 mmol) prepared above. After 2 hours, volatiles are removed under vacuum and the cmde product is purified by silica gel chromatography to afford the desired product (107). Compound (107) (2.0 mmol) is dissolved in THF. Tnmethylsilyl triflate (20 mmol) and lutidine (30 mmol) are added and the reaction is followed by TLC. When judged complete, the mixture is treated with tetrabutylammonium fluoride (30 mmol) and the reaction is followed by TLC. When judged complete, the mixture is diluted two-fold with methanol and heated at refux for 1 hour. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyopholization of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (1051 (100) Example 3: Preparation of (112). a compound of Formula III v la Scheme C A solution of (105) (6 mmol), prepared as descnbed in Example 2. and 6- aminocaproic acid (109) (6 mmol) in DMF The course of the reaction is followed by thin layer chromatography When reaction has occuπed. the reaction mixture is concentrated under reduced pressure to giv e the cmde product The desired compound (110) is obtained by puπfication of the cmde product by use of HPLC Compound (110) (4 0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with compound (103) (4 0 mmol). hydroxybenzotπazole (5 0 mmol), diisopropylethyl amine (4 0 mmol) and PyBOP (4 0 mmol) and the coupling reaction mixture is stiπed overnight at room temperature Volatiles are removed under vacuum and the cmde is fractionated bv reverse-phase HPLC to afford the desired product (111) after lyophohzation of the appropπate fractions Compound (111) (2 0 mmol is dissolved in THF Tnmethylsilyl inflate (20 mmol) and lutidine (30 mmol) are added and the reaction is followed by TLC When judged complete, the mixture is treated with tetrabutylammonium fluoπde (30 mmol) and the reaction followed by TLC When judged complete, the mixture is diluted two-fold with methanol and heated at reflux for 1 hour Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropπate fractions The chemistry is detailed below in the following reaction scheme -10 " XΓX Example 4: Preparation of (203). a compound of Formula l\ v ia Scheme D Compound (201) (1 0 mmol ) is dissolved in toluene, stiπed in an ice water bath, and treated sequentially with K O, (10 mmol) and carbonyldiimidazole (1 0 mmol) The ice bath is removed and the reaction mixture is allowed to warm to room temperature. The imidazolide (202) thus produced is used w ithout further manipulation in the coupling reactions descnbed below . A solution of (202) (1.0 mmol) in toluene/DMF with 1 ,4-dιamιnobutane (106) (0.5 mmol) is heated as necessary in a sealed vessel and the reaction followed by TLC When judged complete, the mixture is partitioned between ethyl acetate and water and the organic phase washed with water, dried over sodium sulfate and the solvent removed in vacuo The residue is purified by silica gel chromatography to afford the title product. Compound (201) is reported in J. Med. Chem. 1998, 41. 3727-3735. The chemistry is detailed below in the following reaction scheme: Example 5: Preparation of (206), a compound of Formula V via Scheme E * Adipic acid (205) (2.0 mmol) is dissolv ed in 10 mL anhydrous dimethylformamide and treated sequentially w ith compound (204) (4 0 mmol ) . hydroxybenzotπazole (5.0 mmol), dusopropylethy 1 amine (4.0 mmol) and P BOP (4.0 mmol) and the coupling reaction mixture is stirred ov ernight at room temperature Volatiles are removed under vacuum and the product is purified by silica gel chromatography to afford the title product Compound (204) is repoπed in J Vied Chem PJ%. 49. ϋ~3-b -1) The chemistry is detailed below in the follow ing reaction scheme (204) " K -I l l - Example 6: Preparation of (208), a compound of Formula VI v ia Scheme F A solution of (202) (6 mmol), prepared as described in Example 4, and 6- aminocaproic acid (109) ( 6 mmol) in toluene/DMF is prepared under argon in a flask equipped with magnetic stiπer and drying tube. The course of the reaction is followed by thin layer chromatography. When reaction has occuπed, the reaction solution is diluted with ethyl acetate and washed with aqueous HCl and then water The organic layer is dned (Na 2 SO 4 ), filtered and concentrated under reduced pressure to give the cmde product. The desired compound (207) is obtained by purification of the cmde product by use of HPLC. Compound (207) (4.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with compound (204) (4.0 mmol), hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol) and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the crude is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (204) is reported in J. Med. Chem. 1996, 49. 673-679. The chemistry is detailed below in the following reaction scheme: (20-) (208) Example 7: Preparation of (303), a compound of Formula VII v ia Scheme G A solution of 20 mmols of compound (301) in DMF ith 10 mmols of 1.6- dibromohexane (302) and 40 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC When reaction has occuπed, the reaction mixture is concentrated under reduced pressure to give the cmde product, which is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropπate fractions Compound (301) is U-57930E and is reported in Antimicrobial Agents Che other., 21 :902-905 (1982) The chemistry is detailed below in the following reaction scheme (301) (303) -U S- Example 8: Preparation of (403). a compound of Formula VIII v i a Scheme H A solut i on of 20 mmols of Streptomy cin (401 ) in DMF w ith 10 mmols of 1.4-dιbromobutane (402) and 40 mmols of potassium carbonate i s heated as 5 necessary and the reaction follow ed by TLC When reaction has occurred the react i on m i xture i s concentrated under reduced pressure to giv e the crude product wh i ch i s fract i onated by rev erse-phase HPLC to afford the title product after lyophohzation of the appropπate fractions 0 The chemistrv is detailed below in the follo ing reacuon sc h eme N - OFC^ O Example 9: Preparation of (404), a compound of Foπnula VIII via Scheme H • Adipic acid (205) (2 0 mmol) is dissolv ed in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotπazole (5.0 mmol), diisopropylethyl amme (4 0 mmol) and PyBOP (4 0 mmol). After stirnng for 15 minutes at room temperature, the activated diacid is treated with Streptomycin (401) (4 0 mmol) and the coupling reaction mixture is stirred overnight at room temperature Volatiles are removed under vacuum and the crude is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropπate fractions The chemistrv is detailed below in the follow ing reaction scheme (404) ~ι r Example 10: Preparation of (406). a compound of Formula IX via Scheme I . 1 ,4-Dιamιnobutane (106) ( 10 mmol) is slumed in methanokanhydrous dimethylformamide, stiπed at room temperature, and treated sequentially w ith diisopropylethyl amine (20 mmol) and Streptomycin (401) (20 mmol) After 2 hours the reaction mixture is cooled in an ice water bath and treated further w ith sodium cyanoborohydride (4.0 mmol) and tπfluoroacetic acid (30 mmol) Aftei 2 additional hours the cmde product is precipitated by dropw ise addition to a ten-foli volume of acetonitnle, and then fractionated by reverse-phase HPLC to afford the 0 title product. The chemistrv is detailed below in the follo ing reaction scheme (406) Example 11: Preparation ol (409), a compound of Formula X via Scheme J. Streptomycin (401) (10 mmol) is slurried in methanokanhydrous dimethylformamide, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (20 mmol) and Fmoc glycinal (101) (10 mmol) (prepared as described by Salvi et al. Tetrahedron Lett. 1994, 35, 1 181-1 184). After 2 hours the reaction mixture is cooled in an ice water bath and treated further with sodium cyanoborohydride (4.0 mmol) and trifluoroacetic acid (30 mmol). After 2 additional hours the cmde product is precipitated by dropwise addition to a ten-fold volume of acetonitrile, and then fractionated by reverse-phase HPLC to afford the desired product (407). The above product (407) is then dissolved in anhydrous dimethylformamide (10 mL), stiπed at room temperature and treated with excess piperidine (1.0 mL). After one hour the cmde products are precipitated by dropwise addition to 100 mL acetonitrile with vigorous stirring. The cmde products are fractionated by reverse- phase HPLC to afford the desired product (408). Compound (408) (20 mmol) is slurried in methanol: anhydrous dimethylformamide, stirred at room temperature, and treated sequentially with diisopropylethyl amine (20 mmol) and Streptomycin (401) (20 mmol). After 2 hours the reaction mixture is cooled in an ice water bath and treated further with sodium cyanoborohydride (4.0 mmol) and trifluoroacetic acid (30 mmol). After 2 additional hours the cmde product is precipitated by dropwise addition to a ten-fold volume of acetonitrile, and then fractionated by reverse-phase HPLC to afford the title product. The chemistry is detailed below in the following reaction scheme: Example 12: Preparation of (504), a compound of Formula XI via Scheme K. Tetracycline (501) (10 mmol) is slurried in methanol :anhydrous dimethylformamide, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (20 mmol) and Fmoc glycinal (101) (10 mmol) (prepared as described by Salvi et al. Tetrahedron Lett. 1994, 35, 1181-1 184). After 2 hours the reaction mixture is cooled in an ice water bath and treated further with sodium cyanoborohydride (4.0 mmol) and trifluoroacetic acid (30 mmol). After 2 additional hours the cmde product is concentrated under reduced pressure and then fractionated by reverse-phase HPLC to afford the desired product (502). The above product (502) is then dissolved in anhydrous dimethylformamide (10 mL), stiπed at room temperature and treated with excess piperidine (1.0 mL). After one hour the cmde product is concentrated under reduced pressure and then fractionated by reverse-phase HPLC to afford the desired product (503). Adipic acid (205) (2.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated diacid is treated with compound (503) (4.0 mmol) and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (501) is reported in Can. J. Chem. 1965, 43, 1382-1388; CAS 1771-31-9, 53864-51-0 The chemistry is detailed below in the following reaction scheme: (501) (502) HA Pipeπdn (503) Exa ple 13: Preparation of (507). a compound of Formula XII via Scheme L. Compound (505) ( 1.0 mmol) is dissolved in toluene, stiπed in an ice/water bath, and treated sequentially with K 2 C0 (10 mmol) and carbonyldiimidazole ( 1.0 mmol). The ice bath is removed and the reaction mixture is allowed to warm to room temperature. The imidazolide (506) thus produced is used without further manipulation in the coupling reactions described below. A solution of (506) (1.0 mmol) in toluene/DMF with 1,4-diaminobutane (106) (0.5 mmol) is heated as necessary in a sealed vessel and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (505) is reported in J. Med. Chem. 1994, 37, 3205-3211. The chemistry is detailed below in the following reaction scheme: CDI, * -CO : , Toluene (506) (507) Example 14: Preparation of (509), a compound of Formula XIII via Scheme M A solution of (506) (6 mmol). prepared as descnbed in Example 13, in toluene DMF with 6-amιnocaproιc acid (109) (6 mmol) is heated as necessary in a sealed vessel and the reaction followed by TLC When judged complete, volatiles are removed under vacuum and the cmde is fractionated by rev erse-phase HPLC to afford the desired product (508) after lyophohzation of the appropriate fractions Compound (508) (4 0 mmol) is dissolv ed in 10 mL anhydrous dimethylformamide and treated w ith compound (503) (4 υ mmol ). prepared as descnbed in Example 12, hydroxybenzotπazole ( 5 (J mmol). dusoprop lethy I amme (4 0 mmol) and PyBOP (4 0 mmol) and the coupling reaction mixture is stiπed overnight at room temperature Volatiles are remo\ ed under \ ac um and the cmde is fractionated by reverse-phase HPLC to afford the title product aftei lyophohzation of the appropπate fractions The chemistrv is detailed below in the follow mg reaction scheme PsBOP HOBl. DIPEA DMF (508) (509) Example 15: Preparation of (605). a compound of Formula XIV via Scheme N. Pristinamycin I (601) (10 mmol) is dissolved in MeOH, stiπed at room temperature and treated sequentially with formalin (1 1 mmol), moφholine (1 1 mmol) and methanesulfonic acid ( 1 mmol), and then heated to 40 °C for 8 hours. The reaction mixture is partitioned between saturated sodium bicarbonate solution and ethyl acetate. The organic phase is dried over anhydrous sodium sulfate, and volatiles removed under reduced pressure to afford cmde morpholine adduct (602) which is used without further purification. Compound (602) is dissolved in ethyl acetate, treated with a mixture of sodium acetate and acetic acid, and heated to 45 °C for 4 hours. The reaction mixture is then washed with sodium bicarbonate solution, dried, filtered, evaporated, and purified by chromatography to afford the desired product (603). Piperazine (5.0 mmol) is dissolved in 10 mL anhydrous tetrahydrofuran and stiπed under nitrogen in a dry ice/acetone bath. A solution of 1.0 M butyl lithium (11 mmol) is added via syringe, and the mixture is stiπed for 15 minutes. At this point a solution of ethylene sulfide (1 1 mmol) in 1 mL anhydrous tetrahydrofuran is added dropwise via syringe over 5 minutes. The reaction mixture is then removed from the cooling bath and allowed to slowly rise to room temperature, where it is stiπed for 2 hours. The reaction mixture is then quenched with ammonium chloride. Volatiles are then removed under reduced pressure and the cmde product is fractionated by silica gel chromatography to afford piperazine thiol (604). A solution of 10 mmols of (603) in acetone with 5 mmols of (604) in acetone is cooled to -20 °C and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (601) (602 AcONa. AcOH H AcOEt. H : θ 45 X (603) Example 16: Preparation of (608), a compound of Formula XV via Scheme O. To a solution of Quinupristin (606) (5 mmol) in water acidified to pH 2 with HCl is added zinc (40 mmol). The reaction mixture is filtered and the filtrate is diluted with Na O j , extracted with CH,C1 2 , dried over MgS0 4 and concentrated. The cmde product is purified by chromatography over silica gel to afford compound (607). Adipic acid (205) (2.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated diacid is treated with compound (607) (4.0 mmol) and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (606) PyBOP, HOBt, DIPEA, DMF Example 17: Preparation of (611), a compound of Formula XVI via Scheme P. A solution of 20 mmols of (603), prepared as described in Example 15, in acetone with 20 mmols of 3-mercaptopropionιc acid (609) is cooled to -20 °C and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde product is purified by chromatography to afford the desired product (610). Compound (610) (4.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with compound (607) (4.0 mmol), prepared as described in Example 16, hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol) and the coupling reaction mixmre is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: --l-H (603) (610) (611) Example 18: Preparation of (613), a compound of Formula XVII via Scheme Q A solution of 20 mmols of Pπstmamycin II (612) in acetone with 10 mmols of (604), prepared as descnbed in Example 15, is cooled to -20 ; C and the reaction followed by TLC. When judged complete, the mixture is partitioned between eth l acetate and water and the organic phase washed with water, dπed o er sodium sulfate and the solvent removed in vacuo. The residue is puπfied by chromatography to afford the title structure. The chemistry is detailed below in the follow in reaction scheme (613) Example 19: Preparation of (616), a compound of Formula XVIII via Scheme R. A solution of 20 mmols of (603) in acetone with 20 mmols of 1,6- hexanedithiol (614) is cooled to -20 °C and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (615) after lyophohzation of the appropriate fractions. A solution of 20 mmols of (615) in acetone with 20 mmols of Pristinamycin II (612) is cooled to -20 °C and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: — 1 - * ->— (603) (615) Example 20: Preparation of (618), a compound of Formula XIX via Scheme S. A solution of 20 mmols of Pristinamycin II (612) in acetone with 20 mmols of 3-mercaptopropionic acid (609) is cooled to -20 °C and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (617) after lyophohzation of the appropriate fractions. Compound (617) (4.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated with compound (607) (4.0 mmol), prepared as described in Example 16, hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol) and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (612) (618) Example 21: Preparation of (702), (703), and (704), compounds of Formula XX via Scheme T. A solution of 20 mmols of Spectinomycin (701) in DMF with 10 mmols of α,α'-dibromo-p-xylene and 40 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the crude is fractionated by reverse-phase HPLC to afford the title products after lyopholization of the appropriate fractions The chemistrv is detailed below in the follow in.; reaction scheme Example 22: Preparation of (806), (807), and (808). Gentamicin C, (801) (10 mmol) is slurried in methanoLanhydrous dimethylformamide, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (60 mmol) and benzaldehyde (50 mmol). After 2 hours the reaction mixture is cooled in an ice water bath and treated further with sodium cyanoborohydride (20 mmol) and trifluoroacetic acid (70 mmol). After 2 additional hours the cmde product is precipitated by dropwise addition to a ten-fold volume of acetonitrile, and then fractionated by reverse-phase HPLC to afford the desired product (802). Compound (802) (10 mmol) is slurried in methanoLanhydrous dimethylformamide, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (20 mmol) and Fmoc glycinal (101) (10 mmol) (prepared as described by Salvi et al. Tetrahedron Lett. 1994, 35, 1181-1184). After 2 hours the reaction mixture is cooled in an ice water bath and treated further with sodium cyanoborohydride (4.0 mmol) and trifluoroacetic acid (30 mmol). After 2 additional hours the cmde product is precipitated by dropwise addition to a ten-fold volume of acetonitrile, and then fractionated by reverse-phase HPLC to afford the desired products (803), (804), and (805). The above separated products (803), (804), and (805) are then individually dissolved in anhydrous dimethylformamide (10 mL), stiπed at room temperature and treated with excess piperidine (1.0 mL). After one hour, the cmde products are concentrated under reduced pressure and then fractionated by reverse-phase HPLC to afford compounds (806), (807), and (808). The chemistry is detailed below in the following reaction scheme: Example 23: Preparation of (803), (804), (805), (813), (814), (815), (816), and (817). Gentamicin C 2 (809) (10 mmol) is slurried in methanoLanhydrous dimethylformamide, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (60 mmol) and benzaldehyde (50 mmol). After 2 hours the reaction mixture is cooled in an ice water bath and treated further with sodium cyanoborohydride (20 mmol) and trifluoroacetic acid (70 mmol). After 2 additional hours the cmde product is precipitated by dropwise addition to a ten-fold volume of acetonitrile, and then fractionated by reverse-phase HPLC to afford the desired product (811). Compound (812) is prepared in the same manner from Gentamicin C 3 (810). Compound (811) (10 mmol) is slurried in methanoLanhydrous dimethylformamide, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (20 mmol) and Fmoc glycinal (101) (10 mmol) (prepared as described by Salvi et al. Tetrahedron Lett. 1994, 35, 1181-1184). After 2 hours the reaction mixture is cooled in an ice water bath and treated further with sodium cyanoborohydride (4.0 mmol) and trifluoroacetic acid (30 mmol). After 2 additional hours the cmde product is precipitated by dropwise addition to a ten-fold volume of acetonitrile, and then fractionated by reverse-phase HPLC to afford the desired products (803), (804), (805), and (813), which are then separated by reverse phase chromatography. Compounds (814), (815), (816), and (817) are prepared and separated in the same manner from (812). The above separated products (803), (804), (805), and (813) are then individually dissolved in anhydrous dimethylformamide (10 mL), stiπed at room temperature and treated with excess piperidine (1.0 mL). After one hour, the cmde products are fractionated by reverse-phase HPLC to afford compounds (806), (807), (808), and (818). Compounds (820), (821), and (822) are prepared and separated in the same manner from (814), (815), (816), and (817), respectively. The chemistry is detailed below in the following reaction scheme: P CHQ_ NaCNBH 3 -H(81I).CHJ(812) R=H (809), CH 3 (810) (813) (805 0 FmocHN 5 (814) (815) NHFmoc (816) (81") (806) (807) (808) (818) (819) (820) Example 24: Preparation of (824), a compound of Formula XXI via Scheme U. Compound (806) (10 mmol), prepared as descnbed in Example 22, is slumed in methanol anhydrous dimethylformamide, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (20 mmol) and Streptomycin (401) (10 mmol) After 2 hours the reaction mixture is cooled in an ice water bath and treated further with sodium cyanoborohydπde (4 0 mmol) and tπfluoroacetic acid (30 mmol) After 2 additional hours the cmde product is precipitated bv dropwise addition to a ten- fold volume of acetonitnle, and then fractionated bv reverse-phase HPLC to afford the desired product (823) A solution of (823) (5 mmol) in methanol is hvdrogenated ov ernight at 35 psi, in the presence of 10% Pd C When judged complete, volatiles are remov ed under vacuum and the cmde is fractionated by reverse-phase HPLC to afrord tl title product after lyophohzation of the appropπate fractions ***NOTE: Compound (806) is shown in the example, but the same procedure can be earned out on compounds (807), (808), (818), (819), (820), (821). (822), and (829) to provide their respective dimers w ith streptomycin The chemistry is detailed below in the following reaction scheme NaCNBH, Example 25: Preparation of (828), a compound of Formula XXII v ia Scheme \ Terephthalic acid (826) (2.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol) After stiπin for 15 minutes at room temperature, the activated diacid is treated w ith compound (806) (4.0 mmol), prepared as described in Example 22, and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (827) after lyophohzation of the appropriate fractions. A solution of (827) (5 mmol) in methanol is hydrogenated overnight at 35 psi, in the presence of 10% Pd/C. When judged complete, volatiles are removed under vacuum and the crude is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. ***NOTE: Compound (806) is shown in the example, but the same procedure can be carried out on compounds (807), (808), (818), (819). (820), (821 ). and (822) to provide their respective dimers. The chemistrv is detailed below in the following reaction scheme: PyBOP, HOB; DIPEA, DMF (806) (828) Example 26 Preparation of (830), a compound of Formula XXIII via Scheme \\ . A solution of 20 mmols of (811), prepared as descnbed in Example 23. in THF with 80 mmols of tnethylamine is treated at room temperature w ith 40 mmols of tπfluoroacetic anhydπde for 1 hour A solution of the resulting product ( 1 1 " mmol) in methanol is hydrogenated overnight at 35 psi, in the presence of 10° u Pd/C The reaction mixture is filtered and the filtrate is concentrated to dr ness The cmde product is punfied by re erse-phase HPLC to afford the desired compound (829) A solution of 20 rnmols of compound (829) in DMF with 10 mmols of 1,6- dibromohexane (302) ind 40 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed undέr vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. ***NOTE: Compound (811) is shown in the example, but the same procedure can be earned out on compounds (802) and (812) to provide the respective products. The chemistry is detailed below in the follow ing reaction scheme (829) (811) (330) Example 27: Preparation of (831), a compound of Formula XXIN via Scheme X. A solution of 20 mmols of compound (829), prepared as described in Example 26, in DMF with 20 mmols of 3-bromopropionic acid (833) and 200 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (834) after lyophohzation of the appropriate fractions. Compound (834) (4.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (806) (4.0 mmol) and the coupling reaction mixture is stiπed overnight at room temperature. The mixture is diluted two-fold with an aqueous NaOH solution (25 mmol) and heated to 50 °C for 1 hour. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. ***NOTE: Compound (806) is shown in the example, but the same procedure can be carried out on compounds (807), (808), (818), (819), (820), (821), and (822) to provide their respective dimers with compound (829). The chemistry is detailed below in the following reaction scheme: Example 28: Preparation of (832), a compound of Formula XXV via Scheme Y. Succinic acid (104) (2.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (2.0 mmol), diisopropylethyl amine (2.0 mmol) and PyBOP (2.0 mmol). After stirring for 15 minutes at room temperature, the activated diacid is treated with compound (408) (2.0 mmol), prepared as described in Example 11, and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (835) after lyophohzation of the appropriate fractions. Compound (835) (4.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated diacid is treated with compound (806) (4.0 mmol), prepared as described in Example 22, and the coupling reaction mixture is stirred overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. A solution of the resulting product (11.7 mmol) in methanol is hydrogenated overnight at 35 psi, in the presence of 10% Pd/C. The reaction mixture is filtered and the filtrate is concentrated to dryness. The cmde product is purified by reverse-phase HPLC to afford the title product. ***NOTE: Compound (806) is shown in the example, but the same procedure can be carried out on compounds (807), (808), (818), (819), (820), (821), and (822) to provide their respective dimers with compound (408). The chemistry is detailed below in the following reaction scheme: (335) (832) Example 29: Preparation of (902), a compound of Formula XXVI via Scheme Z. A solution of 10 mmols of compound (301) in DMF with 10 mmols of 3- bromopropionic acid (833) and 20 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (901) after lyophohzation of the appropriate fractions. Compound (901) (4.0 mmol) is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (103) (4.0 mmol), prepared as described in Example 1 , and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (301) is U-57930E and is reported in Antimicrobial Agents Chemother. 21:902-905 (19892). The chemistry is detailed below in the following reaction scheme: (901) (902) Example 30: Preparation of (905), a compound of Formula XXVII via Scheme AA. 1 ,4-Diaminobutane (106) (4.0 mmol) is dissolved in DMF, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (4.0 mmol) and imidazolide (105) (4.0 mmol), prepared as described in Example 2. After 2 hours, volatiles are removed under vacuum and the cmde product is purified by reverse- phase HPLC to afford the desired product (903). Compound (903) (2.0 mmol) is dissolved in DMF, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (4.0 mmol) and imidazolide (202) (2.0 mmol), prepared as described in Example 4. After 2 hours, volatiles are removed under vacuum and the cmde product is purified by reverse- phase HPLC to afford the desired product (904). Compound (904) (2.0 mmol) is dissolved in THF. Trimethylsilyl triflate (20 mmol) and lutidine (30 mmol) are added and the reaction is followed by TLC. When judged complete, the mixture is treated with tetrabutylammonium fluoride (30 mmol) and the reaction is followed by TLC. When judged complete, the mixture is diluted two-fold with methanol and heated at refux for 1 hour. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (105) Example 31: Preparation of (905), a compound of Formula XXVIII via Scheme BB Succinic acid (104) (8.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (10 mmol), diisopropylethyl. amine (8.0 mmol) and PyBOP (8.0 mmol). After stirring for 15 minutes at room temperature, the diacid is treated with compound (103) (8.0 mmol), prepared as described in Example 1, and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (906) after lyophohzation of the appropriate fractions. Compound (906) (2.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (2.5 mmol), diisopropylethyl amine (2.0 mmol) and PyBOP (2.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (204) (2.0 mmol) and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (204) is reported in J. Med. Chem. 1996, 49, 673-679. The chemistry is detailed below in the following reaction scheme: (103) (906) (907) Example 32: Preparation of (909), a compound of Formula XXIX via Scheme CC. Compound (110) (4.0 mmol), prepared as described in Example 3, is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (204) (4.0 mmol) and the coupling reaction mixture is stirred overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (908) after lyophohzation of the appropriate fractions. Compound (908) (2.0 mmol) is dissolved in THF. Trimethylsilyl triflate (20 mmol) and lutidine (30 mmol) are added and the reaction is followed by TLC. When judged complete, the mixture is treated with tetrabutylammonium fluoride (30 mmol) and the reaction is followed by TLC. When judged complete, the mixture is diluted two-fold with methanol and heated at reflux for 1 hour. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (204) is reported in J. Med. Chem. 1996, 49, 673-679. The chemistry is detailed below in the following reaction scheme: (HO) Example 33: Preparation of (911), a compound of Formula XXX via Scheme DD. A solution of (105) (2.0 mmol), prepared as described in Example 2, in toluene/DMF with 1,4-diaminobutane (106) (2.0 mmol) is heated as necessary in a sealed vessel and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (922) after lyophohzation of the appropriate fractions. A solution of the above product (922) (1.0 mmol) in DMF with compound (202) (1.0 mmol), prepared as described in Example 4, is heated as necessary in a sealed vessel and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (910) after lyophohzation of the appropriate fractions. Compound (910) (2.0 mmol) is dissolved in THF. Trimethylsilyl triflate (20 mmol) and lutidine (30 mmol) are added and the reaction is followed by TLC. When judged complete, the mixture is treated with tetrabutylammonium fluoride (30 mmol) and the reaction is followed by TLC. When judged complete, the mixture is diluted two-fold with methanol and heated at reflux for 1 hour. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (105) (922) 5 (911) Example 34: Preparation of (923) and (924), compounds of Formula XXXI via Scheme EE. A solution of 10 mmols of Spectinomycin (701) in DMF with 10 mmols of 3- bromopropionic acid (833) and 20 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired products (912) and (913) after lyophohzation of the appropriate fractions. Compounds (912) (4.0 mmol) and (913) (4.0 mmol) are individually dissolved in anhydrous dimethylformamide and treated sequentially with compound (103) (4.0 mmol), prepared as described in Example 1, hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol) and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the crude is fractionated by reverse-phase HPLC to afford the title products after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (701) (103) (912) (913) PyBOP, HOBt, DIPΞA, DMF Example 35: Preparation of (915), a compound of Formula XXXII via Scheme FF. 1 ,4-Diaminobutane (106) (4.0 mmol) is dissolved in toluene/DMF, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (4.0 mmol) and imidazolide (105) (4.0 mmol), prepared as described in Example 2. After 2 hours, volatiles are removed under vacuum and the cmde is fractionated by reverse- phase HPLC to afford the desired product (903) after lyophohzation of the appropriate fractions. Compound (903) (2.0 mmol) is dissolved in toluene, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (4.0 mmol) and imidazolide (506) (2.0 mmol), prepared as described in Example 13. After 2 hours, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (914) after lyophohzation of the appropriate fractions. Compound (914) (2.0 mmol) is dissolved in THF. Trimethylsilyl triflate (20 mmol) and lutidine (30 mmol) are added and the reaction is followed by TLC. When judged complete, the mixture is treated with tetrabutylammonium fluoride (30 mmol) and the reaction is followed by TLC. When judged complete, the mixture is diluted two-fold with methanol and heated at reflux for 1 hour. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (506) (914) Example 36: Preparation of (916), a compound of Formula XXXIII via Scheme GG Compound (906) (2 0 mmol), prepared as descnbed in Example 31, is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially w ith hydroxybenzotπazole (2.5 mmol), diisopropylethyl amme (2 0 mmol) and PyBOP (2 0 mmol) After stirnng for 15 minutes at room temperature, the activated acid is treated with compound (503) (2 0 mmol), prepared as descnbed in Example 1 and the coupling reaction mixture is stiπed ov emight at room temperature V olatiles are removed under vacuum and the cmde is fractionated by re erse-phase HPLC to afford the title product after lyophohzation of the appropnate fractions The chemistry is detailed below in the following reaction scheme (906) Example 37: Preparation of (918), a compound of Formula XXXIV via Scheme HH. Compound (110) (4.0 mmol), prepared as described in Example 3, is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (503) (4.0 mmol), prepared as described in Example 12, and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (908) after lyophohzation of the appropriate fractions. Compound (908) (2.0 mmol) is dissolved in THF. Trimethylsilyl triflate (20 mmol) and lutidine (30 mmol) are added and the reaction is followed by TLC. When judged complete, the mixture is treated with tetrabutylammonium fluoride (30 mmol) and the reaction is followed by TLC. When judged complete, the mixture is diluted two-fold with methanol and heated at reflux for 1 hour. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (110) (918) Example 38: Preparation of (921), a compound of Formula XXXV via Scheme II. A solution of compound (922) (1.0 mmol), prepared as described in Example 33, in DMF with compound (506) (1.0 mmol), prepared as described in Example 13, is heated as necessary in a sealed vessel and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (920) after lyophohzation of the appropriate fractions. Compound (920) (2.0 mmol) is dissolved in THF. Trimethylsilyl triflate (20 mmol) and lutidine (30 mmol) are added and the reaction is followed by TLC. When judged complete, the mixture is treated with tetrabutylammonium fluoride (30 mmol) and the reaction is followed by TLC. When judged complete, the mixture is diluted two-fold with methanol and heated at reflux for 1 hour. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (922) (920) -no- Example 39: Preparation of (1001), a compound of Formula XXXVI via Scheme JJ. 3-Bromopropionic acid (833) (4.0 mmol) is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (204) (4.0 mmol) and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde product is purified by silica gel chromatography to afford the desired product (1000). A solution of 2 mmols of the above compound (1000) in DMF with 2 mmols compound (301) and 20 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (204) is reported in J. Med. Chem., 49:673-679 (1996). Compound (301) is U-57930E and is reported in Antimicrobial Agents Chernother, 21 :902-905 (1982). The chemistry is detailed below in the following reaction scheme: (204) (1000) (1001) Example 39A: Preparation of (1012), a compound of Formula XXXVII via Scheme KK. A solution of (202) (20 mmol), prepared as described in Example 4, in DMF with 3-bromopropylamine hydrobromide (1011) (20 mmol) is heated as necessary in a sealed vessel and the reaction followed by TLC. When judged complete, the mixture is partitioned between ethyl acetate and water and the organic phase washed with water, dried over sodium sulfate and the solvent removed in vacuo. The residue is purified by chromatography to afford the desired product (1002). A solution of 10 mmols of the above compound (1002) in DMF with 10 mmols of compound (301) and 20 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (301) is U-57930E and is reported in Antimicrobial Agents Chemother. 1982, 21, 902-905. The chemistry is detailed below in the following reaction scheme: Example 40: Preparation of (1004), a compound of Formula XXXVIII via Scheme LL. A solution of 20 mmols of the compound (301) in DMF with 20 mmols 3- bromoropionic acid (833) and 40 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, the mixture is partitioned between ethyl acetate and water and the organic phase washed with water, dried over sodium sulfate and the solvent removed in vacuo. The residue is purified by chromatography to afford the desired product (1003). The above product (1003) (4.0 mmol) is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (503) (4.0 mmol), prepared as described in Example 12, and the coupling reaction mixture is stirred overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (301) is U-57930E and is reported in Antimicrobial Agents Chemother. 1982, 21, 902-905. The chemistry is detailed below in the following reaction scheme: (1003) (1004) Example 41: Preparation of (1006) and (1007), compounds of Formula XXXIX via Scheme MM. A solution of 20 mmols of compound (301) in DMF with 20 mmols of 1,6- diaminohexane (302) and 40 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (1005) after lyophohzation of the appropriate fractions. A solution of 10 mmols of the above compound (1005) in DMF with 10 mmols of Spectinomycin (701) and 20 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (301) is U-57930E and is reported in Antimicrobial Agents Chemother. 1982, 21, 902-905. (301) (1006) (1007) Example 42: Preparation of (1010), a compound of Formula XL via Scheme NN. A solution of 20 mmols of 6-bromohexanoic acid (1008) in DMF with 20 mmols of compound (301) and 40 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, the reaction mixture is concentrated under reduced pressure and the residue purified by chromatography to afford the desired product (1009). The above compound (1009) (4.0 mmol) is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (503) (4.0 mmol), prepared as described in Example 12, and the coupling reaction mixture is stirred overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (301) is U-57930E and is reported in Antimicrobial Agents Chemother. 1982, 21, 902-905. The chemistry is detailed below in the following reaction scheme: (1009) (1010) Example 43: Preparation of (1101), a compound of Formula XLI via Scheme 00. Compound (906) (4.0 mmol), prepared as described in Example 31, is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mrrol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (607) (4.0 mmol), prepared as described in Example 16. and the coupling reaction mixture is stiπed overnight at room temperature Volatiles are removed under vacuum and the cmde is fractionated by re erse-phase HPLC to afford the title product after lyopholization of the appropriate fractions. The chemistry is detailed below in the follo ing reaction scheme (1101) Exa ple 44: Preparation of (1102), a compound of Foπnula XLII via Scheme PP. Compound (610) (4.0 mmol), prepared as described in Example 17, is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol). diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (103) (4.0 mmol), prepared as described in Example 1. and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: Example 45: Prepara f 'on of (1103), a compound of Formula XLIII via Scheme QQ Compound (617) (4.0 mmol), prepared as described in Example 16. is dissolved in anhydrous dimethylformamide and treated sequentially w ith hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol ) and Py BOP (4.0 mmol). After stirring for 15 minutes at room temperature, the acti ated acid is treated with compound (103) (4.0 mmol), prepared as described in Example 1. and the coupling reaction mixture is stiπed ov ernight at room temperature Volatiles are removed under vacuum and the cmde is fractionated by rev rse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions The chemistrv is detailed below in the following reaction scheme H-v (U03) Example 46: Preparation of (1105), a compound of Formula XLIV via Scheme RR. Compound (901) (4.0 mmol), prepared as described in Example 29. is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (607) (4.0 mmol), prepared as described in Example 16. and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: PyBOP. HOBt. DIPEA. DMF (1105) Example 47: Preparation of (1113), a compound of Formula XLV via Scheme SS. Compound (301) (10 mmol) is slurried in methanol: anhydrous dimethylformamide, stiπed at room temperature, and treated sequentially with diisopropylethyl amine (20 mmol) and Fmoc glycinal (101) (10 mmol) (prepared as described by Salvi et al. Tetrahedron Lett. 1994, 35, 1 181-1184). After 2 hours the reaction mixture is cooled in an ice water bath and treated further with sodium cyanoborohydride (4.0 mmol) and trifluoroacetic acid (30 mmol). After 2 additional hours, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (1106) after lyophohzation of the appropriate fractions. The above product (1106) is then dissolved in anhydrous dimethylformamide (10 mL), stiπed at room temperature and treated with excess piperidine (1.0 mL). After one hour the cmde products are fractionated by reverse-phase HPLC to afford the desired product (1112). Compound (617) (4.0 mmol), prepared as described in Example 20, is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (1112) (4.0 mmol) and the coupling reaction mixture is stirred overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyopholization of the appropriate fractions. Compound (301) is U-57930E and is reported in Antimicrobial Agents Chemother. 1982, 21, 902-905. The chemistry is detailed below in the following reaction scheme: (301) (617) (1112 PyBOP, HOB:. DIPEA, DMF Example 48: Preparation of (1108), a compound of Formula XLVI via Scheme TT. Compound (204) (10 mmol) is dissolved in anhydrous dimethylformamide and treated with adipic acid (205) (10 mmol), hydroxybenzotriazole (10 mmol), diisopropylethyl amine (20 mmol) and PyBOP (10 mmol) and the coupling reaction mixture is stirred overnight at room temperature. After deprotection with NaOH, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (1107) after lyophohzation of the appropriate fractions. The above compound (1107) (4.0 mmol) is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (607) (4.0 mmol), prepared as described in Example 16, and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (204) is reported in J. Med. Chem. 1996, 49, 673-679. The chemistry is detailed below in the following reaction scheme: (1107) (1108) Example 49: Preparation of (1109), a compound of Formula XL VII via Scheme UU. Compound (207) (4.0 mmol), prepared as described in Example 6, is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (607) (4.0 mmol), prepared as described in Example 16, and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: PvBOP. HOBt. DIPEA. DMF (1109) Example 50: Preparation of (1110), a compound of Formula XL VIII via Scheme W. Compound (610) (4.0 mmol), prepared as described in Example 17, is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (204) (4.0 mmol), prepared as described in Example 16, and the coupling reaction mixture is stirred overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (204) is reported in J. Med. Chem. 1996, 49, 673-679. The chemistry is detailed below in the following reaction scheme: ) (1110) Example 51: Preparation of (1111), a compound of Formula XLIX via Scheme WW. Compound (617) (4.0 mmol), prepared as described in Example 20, is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (204) (4.0 mmol), prepared as described in Example 16, and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (204) is reported in J. Med. Chem. 1996, 49, 673-679. The chemistry is detailed below in the following reaction scheme: Exa ple 52: Preparation of (1201), a compound of Formula L via Scheme XX. A solution of 20 mmols of compound (829), prepared as described in Example 26, in DMF with 20 mmols of 1 ,6-dibromohexane (302) and 40 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, the cmde product is purified by chromatography to afford the desired product (1200). A solution of 10 mmols of the above compound (1200) in DMF with 10 mmols of compound (301) and 20 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, the reaction mixture is diluted two-fold with water, treated with NaOH (50 mmol), and heated as necessary to effect deprotection. The cmde product is fractionated by reverse- phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (301) is U-57930E and is reported in Antimicrobial Agents Chemother. 1982, 21, 902-905. The chemistry is detailed below in the following reaction scheme: (1201) Example 53: Preparation of (1202) and (1203), compounds of Formula LI via Scheme YY. A solution of 20 mmols of the compound (1200), prepared as described in Example 52, in DMF with 20 mmols of Spectinomycin (701) and 20 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, the reaction mixture is diluted two-fold with water, treated with NaOH (50 mmol), and heated as necessary to effect deprotection. The cmde product is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (1202) (1203) Example 54: Preparation of (1205) and (1206), compounds of Formula LII via Scheme ZZ. A solution of 20 mmols of compound (301) in DMF with 20 mmols of 1,6- dibromohexane (302) and 40 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed under reduced pressure to afford the desired product (1204), which is used in the next step without any further purification. A solution of 10 mmols of the above compound (1204) in DMF with 10 mmols of Spectinomycin (701) and 20 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. Compound (301) is U-57930E and is reported in Antimicrobial Agents Chemother. 1982, 21, 902-905. The chemistry is detailed below in the following reaction scheme: (301) (1204) (1205) (1206) Example 55: Preparation of (1207) and (1208), compounds of Formula LIU via Scheme AAA. Compounds (912) (4.0 mmol) and (913) (4.0 mmol), prepared as described in Example 34, are individually dissolved in anhydrous dimethylformamide and treated with compound (408) (4.0 mmol), prepared as described in Example 11, hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol) and the coupling reaction mixture is stirred overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title products after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: PyBOP, HOBt. DIPEA. DMF (912) (913) (1207) (1208) Example 56: Preparation of (1211), a compound of Formula LIV via Scheme BBB. In a sealed tube, 1,3-phenylenediisocyanate (1209) (41.0 mmol) is dissolved in anhydrous acetonitrile. To this solution is added compound (408) (41.0 mmol), prepared as described in Example 11, and the tube is partially immersed in a silicon oil bath and heated to 65 °C and allowed to stir for 16h. The reaction mixture is cooled and then evaporated to afford the cmde product (1210), which is used in the next step without any further purification. In a sealed tube, compound (1210) (30.0 mmol) is dissolved in anhydrous acetonitrile. To this solution is added compound (503) (30.0 mmol), prepared as described in Example 12, and the tube is partially immersed in a silicon oil bath and heated to 85 °C and allowed to stir for 16h. The reaction mixture is cooled and then evaporated to afford the cmde product, which is purified by reverse-phase HPLC to afford the title product The chemistry is detailed below in the following reaction scheme: (408) (1210) (1211) Example 56A: Preparation of (1213), a compound of Formula LV via Scheme CCC. Succinic acid (104) (8.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (10.0 mmol), diisopropylethyl amine (8.0 mmol) and PyBOP (8.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (835) (8.0 mmol), prepared as described in Example 28, and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the desired product (1212) after lyophohzation of the appropriate fractions. The above compound (1212) (4.0 mmol) is dissolved in 10 mL anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (503) (4.0 mmol), prepared as described in Example 12, and the coupling reaction mixture is stiπed overnight at room temperature. Volatiles are removed under vacuum and the cmde is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: 0= OH (1212) (1213) Example 57: Preparation of (1215), a compound of Formula LVI via Scheme DDD. A solution of 10 mmols of compound (829), prepared as described in Example 26, in DMF with 10 mmols of 6-bromohexanoic acid (1008) and 20 mmols of potassium carbonate is heated as necessary and the reaction followed by TLC. When judged complete, the reaction mixture is concentrated under reduced pressure and the residue purified by chromatography to afford the desired product (1214). The above compound (1214) (4.0 mmol) is dissolved in anhydrous dimethylformamide and treated sequentially with hydroxybenzotriazole (5.0 mmol), diisopropylethyl amine (4.0 mmol) and PyBOP (4.0 mmol). After stirring for 15 minutes at room temperature, the activated acid is treated with compound (503) (4.0 mmol), prepared as described in Example 12, and the coupling reaction mixture is stiπed overnight at room temperature. The reaction mixture is diluted two- fold with water, treated with NaOH (50 mmol), and heated as necessary to effect deprotection. The cmde product is fractionated by reverse-phase HPLC to afford the title product after lyophohzation of the appropriate fractions. The chemistry is detailed below in the following reaction scheme: (829) (1214) 0=-. OH (1215)

Claims: WHAT IS CLAIMED IS: 1. A multibinding compound comprising from 2 to 10 ligands covalently attached to one or more linkers wherein each of said ligands independently comprises a macrolide antibiotic, aminoglycoside, hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA and/or one or more proteins in the ribosome; and pharmaceutically-acceptable salts thereof. 2. A multibinding compound of formula I: (L) p (X) q wherein each L is independently a ligand which is a macrolide antibiotic, aminoglycoside, hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium ; each X is independently a linker; p is an integer of from 2 to 10; and q is an integer of from 1 to 20; and pharmaceutically-acceptable salts thereof. 3. The multibinding compound of Claim 2 wherein q is less than/ * . 4. The multibinding compound of Claim 3 wherein each ligand is independently selected from the group consisting of: Erytbromy α Clindamycin Linezolid Quinupristin Tetracycline Gentamicin Streptomycin 5. The multibinding compound of Claim 4 wherein each linker independently has the formula: -X a -Z-(Y a -Z) m -Y D -Z-X a - wherein m is an integer of from 0 to 20; X a at each separate occuπence is selected from the group consisting of -O-, -S-, -NR-, -C(O)-, -C(0)0-, -C(O)NR-, -C(S), -C(S)0-, -C(S)NR- or a covalent bond where R is as defined below; Z is at each separate occuπence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, or a covalent bond; Y a and Y b at each separate occurrence are selected from the group consisting of -C(O)NR'-, -NR'C(O)-, -NR'C(0)NR'-, -C(=NR')-NR'-, -NR'-C(=NR')-, -NR'-C(0)-0-, -N=C(X a )-NR'-, -P(0)(OR')-O-, -S(O) n CR'R"-, -S(0) n -NR'-, -S-S- and a covalent bond; where n is 0, 1 or 2; and R, R' and R" at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic. 6. A multibinding compound of formula II: L'- X'- L' II wherein each L' is independently a ligand comprising a macrolide antibiotic, aminoglycoside, hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium and X' is a linker; and pharmaceutically-acceptable salts thereof. " 7. The multibinding compound of Claim 6 wherein each ligand is 5 independently selected from tlivi group consisting of 8. The multibinding compound of Claim 7 wherein X' has the formula: -X a -Z-(Y a -Z) m -Y b -Z-X a - wherein m is an integer of from 0 to 20; X a at each separate occuπence is selected from the group consisting of -O-, -S-, -NR-, -C(O)-, -C(0)0-, -C(0)NR-, -C(S), -C(S)0-, -C(S)NR- or a covalent bond where R is as defined below; Z is at each separate occuπence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, or a covalent bond; Y a and Y b at each separate occuπence are selected from the group consisting of -C(O)NR'-, -NR'C(O)-, -NR'C(0)NR'-, -C(=NR')-NR'-, -NR'-C(-NR')-, -NR'-C(0)-0-, -N * =C(X a )-NR'-, -P(O)(OR')-0-, -S(O) n CR'R"-, -S(O) n -NR'-, -S-S- and a covalent bond; where n is 0, 1 or 2; and R, R' and R" at each separate occuπence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic. 9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a multibinding compound comprising from 2 to 10 ligands covalently attached to one or more linkers wherein each of said ligands independently comprises a macrolide antibiotic, aminoglycoside, Hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium; and pharmaceutically-acceptable salts thereof. 10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a multibinding compound of formula I: (L)„(X) α wherein each L is independently a ligand comprising a macrolide antibiotic, aminoglycoside, Hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium; each X is independently a linker; * is an integer of from 2 to 10; and q is an integer of from 1 to 20; and pharmaceutically-acceptable salts thereof. 11. The pharmaceutical composition of Claim 10 wherein q is less than/?. 12. The pharmaceutical composition of Claim 1 1 wherein each ligand is independently selected from the group consisting of Erytbromyciα Clindamycin Linezolid Spectinomycin Dalfopristin Quiπupristin Tetracycline Gentamicin Streptomycin 13. The pharmaceutical composition of Claim 12 wherein each linker independently has the formula: -X a -Z-(Y a -Z) m -Y b -Z-X a - wherein m is an integer of from 0 to 20; X a at each separate occuπence is selected from the group consisting of -O-, -S-, -NR-, -C(O)-, -C(O)O-, -C(O)NR-, -C(S), -C(S)0-, -C(S)NR- or a covalent bond where R is as defined below; Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, or a covalent bond; Y a and Y b at each separate occuπence are selected from the group consisting of -C(O)NR'-, -NR'C(O)-, -NR'C(O)NR'-, -C(=NR')-NR'-, -NR'-C(=NR')-, -NR'-C(O)-O-, -N=C(X a )-NR'-, -P(O)(OR')-O-, -S(O) n CR'R"-, -S(O) n -NR'-, -S-S- and a covalent bond; where n is 0, 1 or 2; and R, R' and R" at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic. 14. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a multibinding compound of formula II: L'- X'- L' II wherein each L' is independently a ligand comprising a macrolide antibiotic, aminoglycoside, Hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA or to one or more proteins involved in ribosomal protein synthesis in the bacterium; and X' is a linker; and pharmaceutically-acceptable salts thereof. 5 15. The pharmaceutical composition of Claim 14 wherein each ligand is independently selected from the group consisting of Clindamycin Linezolid Spectii Dalfopristin Quinupriitin 16. The pharmaceutical composition of Claim 15 wherein X' has the formula: -X J -Z-(Y a -Z) m -Y b -Z-X α - wherein m is an integer of from 0 to 20; X a at each separate occuπence is selected from the group consisting of -0-, -S-, -NR-, -C(O)-. -C(0)0-, -C(0) R-. -C(S), -C(S)0-, -C(S)\ ' R- or a covalent bond where R is as defined below; Z is at each separate occuπence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene. substituted cylcoalkylene. alkenylene, substituted alkenylene, alkynylene, substituted alkynylene. cycloalkenylene, substituted cycloalkenylene. arylene. heteroarylene. heterocyclene, or a covalent bond; Y a and Y b at each separate occuπence are selected from the group consisting of-C(0)NR'-, -NR'C(O)-. -NR'C(0) R\ -C^NTO-NTT-. -NR'-C(=NR>, -NR'-C(0)-0-, -NKTO-NR'-, -P(O)(OR ' )-O-, -S(0) n CR'R"-, -S(O) n - R'-, -S-S- and a covalent bond; where n is 0, 1 or 2; and R, R' and R" at each separate occuπence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl. substituted cycloalkyl. alkenyl. substituted alkenyl, cycloalkenyl, substituted cycloalkenyl. alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic. 17. A method for treating bacterial infections in a patient comprising administering an effective, antibacterial amount of a compound of claim I to a patient in need of treatment thereof. 18. The method of claim 17 wherein the compound is of the following formula: wherein each L is independently a ligand which is a macrolide antibiotic, aminoglycoside, hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA or to one or more proteins involved in ribosomal protein synthesis in the bacterium; each X is independently a linker; p is an integer of from 2 to 10; and q is an integer of from 1 to 20; and pharmaceutically-acceptable salts thereof. 19. The method of claim 18 wherein q is less than p. 20. The method of claim 19 wherein each ligand is independently selected from the group consisting of: Erytbromydo Clindamycin Linezolid Spectinomycin Tetracycline Streptomycin 21. The method of claim 18 wherein each linker independently has the foπnula: -X a -Z-(Y a -Z) m -Y b -Z-X a - wherein m is an integer of from 0 to 20; X a at each separate occuπence is selected from the group consisting of -O-, -S-, -NR-, -C(O)-, -C(O)O-, -C(O)NR-, -C(S), -C(S)0-, -C(S)NR- or a covalent bond where R is as defined below; Z is at each separate occuπence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, or a covalent bond; Y a and Y b at each separate occuπence are selected from the group consisting of -C(O)NR'-, -NR'C(O)-, -NR'C(O)NR\ -C(=NR')-NR'-, -NR'-C(=NR , -NR'-C(O)-O-, -N=C(X a )-NR'-, -P(O)(OR')-O-, -S(O) n CR'R"-, -S(O) n -NR'-, -S-S- and a covalent bond; where n is 0, 1 or 2; and R, R' and R" at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic. 22. The method of claim 17 wherein the compound has the following formula: L'- X'- L' II wherein each L' is independently a ligand comprising a macrolide antibiotic, aminoglycoside, Hncosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium and X' is a linker; and pharmaceutically-acceptable salts thereof. 23. The method of claim 22 wherein each ligand is independently 5 selected from the group consisting of Erytbromydn CUad myein Linezolid Quinupristin 24. The method of claim 22 wherein X' has the formula: -X a -Z-(Y a -Z) m -Y b -Z-X a - wherein m is an integer of from 0 to 20; X at each separate occuπence is selected from the group consisting of -O-, -S-, -NR-, -C(O)-, -C(O)0-, -C(O)NR-, -C(S), -C(S)0-, -C(S)NR- or a covalent bond where R is as defined below; Z is at each separate occuπence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, or a covalent bond; Y a and Y b at each separate occurrence are selected from the group consisting of-C(O)NR'-, -NR'C(O)-, -NR'C(O)NR'-, -C(=NR')-NR'-, -NR'-C(=NR')-, -NR'-C(O)-0-, -N=C(X a )-NR'-, -P(0)(OR')-O-, -S(O) n CR'R"-, -S(O) n -NR'-, -S-S- and a covalent bond; where n is 0, 1 or 2; and R, R' and R" at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic. 25. A method for identifying multimeric ligand compounds possessing multibinding properties which method comprises: (a) identifying a ligand or a mixture of ligands wherein each ligand binds to bacterial ribosomal RNA and/or one or more proteins involved in ribosomal protein synthesis and contains at least one reactive functionality; (b) identifying a library of linkers wherein each linker in said library comprises at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand; (c) preparing a multimeric ligand compound library by combining at least two stoichiometric equivalents of the ligand or mixture of ligands identified in (a) with the library of linkers identified in (b) under conditions wherein the complementary functional groups react to form a covalent linkage between said linker and at least two of said ligands; and (d) assaying the multimeric ligand compounds produced in the library prepared in (c) above to identify multimeric ligand compounds possessing multibinding properties. 26. A method for identifying multimeric ligand compounds possessing multibinding properties which method comprises: (a) identifying a library of ligands wherein each ligand binds to bacterial ribosomal RNA and/or one or more proteins involved in ribosomal protein synthesis and contains at least one reactive functionality; (b) identifying a linker or mixture of linkers wherein each linker comprises at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand; (c) preparing a multimeric ligand compound library by combining at least two stoichiometric equivalents of the library of ligands identified in (a) with the linker or mixture of linkers identified in (b) under conditions wherein the complementary functional groups react to form a covalent linkage between said linker and at least two of said ligands; and (d) assaying the multimeric ligand compounds produced in the library prepared in (c) above to identify multimeric ligand compounds possessing multibinding properties. 27. The method according to Claim 25 or 26 wherein the preparation of the multimeric ligand compound library is achieved by either the sequential or concurrent combination of the two or more stoichiometric equivalents of the ligands identified in (a) with the linkers identified in (b). 28. The method according to Claim 27 wherein the multimeric ligand compounds comprising the multimeric ligand compound library are dimeric. 29. The method according to Claim 28 wherein the dimeric ligand compounds comprising the dimeric ligand compound library are heteromeric. 30. The method according to Claim 29 wherein the heteromeric ligand compound library is prepared by sequential addition of a first and second ligand. 31. The method according to Claim 25 or 26 wherein, prior to procedure (d), each member of the multimeric ligand compound library is isolated from the Hbrary. 32. The method according to Claim 31 wherein each member of the library is isolated by preparative liquid chromatography mass spectrometry (LCMS). 33. The method according to Claim 25 or 26 wherein the linker or linkers employed are selected from the group comprising flexible linkers, rigid linkers, hydrophobic linkers, hydrophilic linkers, linkers of different geometry, acidic linkers, basic linkers, linkers of different polarizability and/or polarization and/or polarizability and amphiphilic linkers. 34. The method according to Claim 33 wherein the linkers comprise linkers of different chain length and/or having different complementary reactive groups. 35. The method according to Claim 34 wherein the linkers are selected to have different linker lengths ranging from about 2 to 100A. 36. The method according to Claim 25 or 26 wherein the ligand or mixture of ligands is selected to have reactive functionality at different sites on said ligands. 37. The method according to Claim 36 wherein said reactive functionality is selected from the group consisting of carboxylic acids, carboxylic acid halides, carboxyl esters, amines, halides, pseudohalides, isocyanates, vinyl unsaturation, ketones, aldehydes, thiols, alcohols, anhydrides, boronates, and precursors thereof wherein the reactive functionality on the ligand is selected to be complementary to at least one of the reactive groups on the linker so that a covalent linkage can be formed between the linker and the ligand. 38. The method according to Claim 25 or 26 wherein the multimeric ligand compound library comprises homomeric ligand compounds. 39. The method according to Claim 25 or 26 wherein the multimeric ligand compound library comprises heteromeric ligand compounds. 40. A library of multimeric ligand compounds which may possess multivalent properties which library is prepared by the method comprising: (a) identifying a ligand or a mixture of ligands wherein each Hgand binds to bacterial ribosomal RNA and/or one or more proteins involved in ribosomal protein synthesis and contains at least one reactive functionality; (b) identifying a library of linkers wherein each linker in said library comprises at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand; and (c) preparing a multimeric ligand compound library by combining at least two stoichiometric equivalents of the Hgand or mixture of ligands identified in (a) with the library of linkers identified in (b) under conditions wherein the complementary functional groups react to form a covalent linkage between said linker and at least two of said ligands. 41. A library of multimeric ligand compounds which may possess multivalent properties which library is prepared by the method comprising: (a) identifying a library of ligands wherein each ligand binds to bacterial ribosomal RNA and/or one or more proteins involved in ribosomal protein synthesis and contains at least one reactive functionality; (b) identifying a linker or mixture of linkers wherein each linker comprises at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand; and (c) preparing a multimeric ligand compound library by combining at least two stoichiometric equivalents of the library of ligands identified in (a) with the linker or mixture of linkers identified in (b) under conditions wherein the complementary functional groups react to form a covalent linkage between said linker and at least two of said ligands. 42. The library according to Claim 40 or 41 wherein the linker or linkers employed are selected from the group comprising flexible linkers, rigid linkers, hydrophobic linkers, hydrophilic linkers, linkers of different geometry, acidic linkers, basic linkers, linkers of different polarizability and/or polarization and amphiphilic linkers. 43. The library according to Claim 42 wherein the linkers comprise linkers of different chain length and/or having different complementary reactive groups. 44. The library according to Claim 43 wherein the linkers are selected to have different linker lengths ranging from about 2 to 100A. 45. The library according to Claim 40 or 41 wherein the Hgand or mixture of ligands is selected to have reactive functionality at different sites on said Hgands. 46. The library according to Claim 45 wherein said reactive functionality is selected from the group consisting of carboxylic acids, carboxylic acid halides, carboxyl esters, amines, halides, pseudohalides, isocyanates, vinyl unsaturation, ketones, aldehydes, thiols, alcohols, anhydrides, boronates, and precursors thereof wherein the reactive functionality on the ligand is selected to be complementary to at least one of the reactive groups on the linker so that a covalent linkage can be formed between the linker and the ligand. 47. The library according to Claim 41 or 42 wherein the multimeric ligand compound Hbrary comprises homomeric ligand compounds. 48. The library according to Claim 40 or 41 wherein the multimeric ligand compound library comprises heteromeric ligand compounds. 49. An iterative method for identifying multimeric ligand compounds possessing multibinding properties which method comprises: (a) preparing a first collection or iteration of multimeric compounds which is prepared by contacting at least two stoichiometric equivalents of the ligand or mixture of ligands which target a receptor with a linker or mixture of linkers wherein said ligand or mixture of ligands binds to bacterial ribosomal RNA and/or one or more proteins involved in ribosomal protein synthesis and comprises at least one reactive functionality and said linker or mixture of linkers comprises at least two functional groups having complementary reactivity to at least one of the reactive functional groups of the ligand wherein said contacting is conducted under conditions wherein the complementary functional groups react to form a covalent linkage between said linker and at least two of said Hgands; (b) assaying said first collection or iteration of multimeric compounds to assess which if any of said multimeric compounds possess multibinding properties; (c) repeating the process of (a) and (b) above until at least one multimeric compound is found to possess multibinding properties; (d) evaluating what molecular constraints imparted or are consistent with imparting multibinding properties to the multimeric compound or compounds found in the first iteration recited in (a)- (c) above; (e) creating a second collection or iteration of multimeric compounds which elaborates upon the particular molecular constraints imparting multibinding properties to the multimeric compound or compounds found in said first iteration; (f) evaluating what molecular constraints imparted or are consistent with imparting enhanced multibinding properties to the multimeric compound or compounds found in the second collection or iteration recited in (e) above; (g) optionally repeating steps (e) and (f) to further elaborate upon said molecular constraints. 50. The method according to Claim 49 wherein steps (e) and (f) are repeated from 2-50 times. 51. The method according to Claim 50 wherein steps (e) and (f) are repeated from 5-50 times.

Inventors: GRIFFIN JOHN H, PACE JOHN L, GRIFFIN, JOHN, H., PACE, JOHN, L.
Applicants: ADVANCED MEDICINE INC, GRIFFIN JOHN H, PACE JOHN L, ADVANCED MEDICINE, INC., GRIFFIN, JOHN, H., PACE, JOHN, L.
Application year: 1999
Main classification: A61K
IPC codes: A01N57, A61K31, A61K38, A61K39, A61K47, A61K51, A61P31, A61P43, C07B61, C07C233, C07C237, C07C271, C07C275, C07C335, C07D207, C07D211, C07D215, C07D233, C07D235, C07D263, C07D265, C07D401, C07D405, C07D413, C07D453, C07D471, C07D473, C07D475, C07D477, C07D487, C07D493, C07D495, C07D498, C07D499, C07D501, C07D519, C07H15, C07H17, C07H19, C07K2, C07K4, C12N9, C12P19, C12Q1, C40B30, C40B40, G01N33, G01N37