OXAZOLIDINONE PHOTOAFFINITY PROBES, USES AND COMPOUNDS

Abstract: Disclosed are novel methods of identifying biological targets of compounds that have antimicrobial activity. Also disclosed are novel methods of identifying compounds that can have antimicrobial activity.

Description: OXAZOLIDINONE PHOTOAFFINITY PROBES, USES AND COMPOUNDS FIELD OF THE INVENTION The present invention is directed, in part, to novel methods of using photoaffinity probes for locating relevant antibiotic binding sites within sensitive cells. In particular, the photoaffinity probes are oxazolidinone photoaffinity probes that are used to identify biological targets of oxazolidinone class of antibiotics. The invention is also directed, in part, to methods of identifying compounds that inhibit binding of a probe to a biological target. BACKGROUND OF THE INVENTION A number of compounds have been recently developed and have been shown to act as antimicrobial or antibacterial agents. International Publication WO 99/41244 discloses substituted aminophenyl isoxazoline compounds useful as antimicrobial agents. U. S. Patent No. 5,910,504 describes hetero-aromatic ring substituted phenyloxazolidinone antimicrobial agents. In addition, International Publication WO 00/10566 discloses isoxazolinone antibacterial agents. An important step in the development of new antimicrobial or antibacterial agents, such as those disclosed above, is the elucidation of a mechanism of action. The specific site of interaction of non selective antibiotics/antitumor agents, such as sparsomycin, that inhibit protein translation by a different, less useful, and direct mechanism, has been described. Porse et al., Proc. Natl. Acad. Sci. USA, 1999,96, 9003-9008. Previous studies with chemical probes using isolated, cell-free systems have failed to define the relative sites of interaction of these types of antibiotic compounds of the oxazolidinone class. Matassova, et al., RNA, 1999,5,939-946. This is, in part, because the previous methods were incapable of defining the sites of the particular and specific mechanism of action of this important class of antibiotics. Probes that help to elucidate the mechanism of action of antimicrobial and/or antibacterial agents and methods of using the same are highly desired. The present invention is directed, inter alia, to novel methods of identifying biological targets of an oxazolidinone-type antibiotic, as well as to methods of identifying compounds that inhibit binding of a probe to a biological target thereof. The present invention comprises use of compounds/probes by a novel mechanism of study that allows the identification of the specific oxazolidinone interaction site (s) within sensitive cells. Applicants'methods comprise using particular compounds in intact cells using competition for the cross-linking to specific sites by active and inactive enantiomers of relevant compounds. These and other aspects of the invention are described below. SUMMARY OF THE INVENTION The present invention is directed to, inter alia, identification of oxazolidinone binding sites within a cell, such as gram-positive and gram-negative bacteria, as well as mammalian cells. The present invention is also directed to screening compounds for antimicrobial activity. In particular, the present invention is directed to methods for identifying a biological target of an oxazolidinone-type antibiotic comprising the steps of contacting a susceptible cell with an oxazolidinone photoaffinity probe, exposing the photoaffinity probe to light to form a complex between the photoaffinity probe and at least one biological target, and detecting the complex. Another embodiment of the invention is directed to methods of identifying a compound that inhibits binding of a probe to a biological target thereof comprising the steps of contacting the biological target with a probe, wherein the biological target is ribosomal RNA, tRNA, LepA, L27, or any combination thereof, contacting the biological target with a test compound, and comparing the amount of binding between the probe and the biological target in the presence and absence of the test compound, wherein a decrease in the amount of binding between the probe and the biological target in the presence of the test compound indicates that the test compound inhibits binding of the probe to the biological target. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS Various definitions are made throughout this document. Most words have the meaning that would be attributed to those words by one skilled in the art. Words specifically defined either below or elsewhere in this document have the meaning provided in the context of invention as a whole and as are typically understood by those skilled in the art. The present invention has identified a specific site of interaction of these specific antibiotics as near the peptidyl transfer center of the ribosome but involving interaction in a manner different than that described for other inhibitors of protein translation. Interaction of these oxazolidinone antibiotics involves the central region V of the 23S RNA together with tRNA, and two proteins of 64 kDa (LepA) and 11 kDa (L27). Identification of relevant sites with this novel approach (compounds and technique) now allows for directed discovery mechanisms using structure-based design together with interaction screens with these specific targets. In particular, the methods of the present invention can be used to identify cellular components that bind to oxazolidinone-type antibiotics and, thus, serve as targets for oxazolidinone-type antibiotics. In addition, the methods of the present invention can be used to screen, for example, libraries of compounds, in order to identify compounds that inhibit binding of a photoaffinity probe, for example, to a biological target thereof. Such compounds can have antibacterial or antimicrobial activity themselves or can be used to design compounds having antibacterial or antimicrobial activity. As used herein, the phrase"biological target"means any protein, nucleic acid, lipid, etc. within a cell. Biological targets include, but are not limited to, the contents of the cytoplasm, nucleus, cell membrane, cell wall, and the like. In particular, biological targets include, but are not limited to, ribosomal RNA, tRNA, LepA protein and L27. Biological targets are capable of binding a probe. As used herein, the term"contacting"means either direct or indirect, application of a probe or test compound within a cell, on or to a cell, or to biological targets from a cell in vitro or in vivo or ex vivo. The test compound and probe can be present within a buffer, salt, solution, etc. As used herein, the term"cross-linking"or"binding"means the physical interaction between a probe and at least one biological target within a cell or from a cell or combinations thereof. Binding includes ionic, non-ionic, Hydrogen bonds, Van der Waals, hydrophobic interactions, etc. The physical interaction, the binding, can be either direct or indirect through or because of another protein or compound. Direct binding refers to interactions that do not take place through or because of another protein or compound but instead are without other substantial chemical intermediates. As used herein, the term"oxazolidinone"means a compound of the class known as oxazolidinones, including the compounds described in U. S. Serial Numbers 07/438, 759, 07/553,795,07/786,107,07/831,213,08/329,717,07/909,387,60/015,499,09/138,209, 60/008,554,60/064,738,60/065,376,60/067,830,60/089,498,60/100,185,60/088,283, 60/092,765,07/244,988,07/253,850; European Patents EP 0500686, EP 0610265, EP 0673370; PCT Application Numbers PCT/US90/06220, PCT/US94/08904, PCT/US94/10582, PCT/US95/02972, PCT/US95/10992, PCT/US93/04850, PCT/US95/12751, PCT/US96/00718, PCT/US93/03570, PCT/US93/09589, PCT/US96/05202, PCT/US97/03458, PCT/US96/12766, PCT/US97/01970, PCT/US96/14135, PCT/US96/19149, PCT/US96/17120, PCT/US98/09889, PCT/US98/13437 ; and U. S. Patent Numbers 5,700,799,5,719,154,5,547,950,5,523,403, 5,668,286,5,652,238,5,688,792,5,247,090,5,231,188,5,654,428,5,654,435,5,756,732, 5,164,510,5,182,403,5,225,565,5,618,949,5,627,197,5,534,636,5,532,261,5,776,937, 5,529,998,5,684,023,5,627,181,5,698,574,5,220,011,5,208,329,5,036,092,4,965,268, 4,921,869,4,948,801,5,043,443,5,130,316,5,254,577,4,877,892,4,791,207,4,642,351, 4,665,171,4,734,495,4,775,752,4,870,169,4,668,517,4,340,606,4,362,866,4,193,918, 4,000,293,3,947,465,4,007,168,3,674,780,3,686,170,3,906,101,3,678,040,3,177,114, 3,141,889,3,149,119,3,117,122,5,719,154,5,254,577,4,801,600,4,705,799,4,461,773, 4,243,801,3,794,665,3,632,577,3,598,830,3,513,238,3,598,812,3,546,241,3,318,878, 3,322,712,5,565,571,5,880,118,5,952,324,5,910,504,6,166,056,5,968,962,6,090,820, 5,736,545,6,277,985,5,955,460,5,922,7076,255,304,6,218,413,5,977,373,6,251,869, 5,929,248, and 5,801,246; the disclosures of each of which are incorporated herein by reference in their entirety. Preferred oxazolidinones include linezolid and eperezolid. As used herein, the term"oxazolidinone-type antibiotic"means any compound having antimicrobial activity and which binds to or interacts with a biological target (proteins, nucleic acids, etc.) of an oxazolidinone antibiotic. Thus, the oxazolidinone-type antibiotic may have the same mechanism of action as an oxazolidinone antibiotic. Alternately, the oxazolidinone-type antibiotic may interact with or bind to some of the same biological targets as does an oxazolidinone antibiotic. Further, the oxazolidinone-type antibiotic may have a chemical structure that is different from an oxazolidinone antibiotic. As used herein, the term"probe"means any compound, protein, nucleic acid molecule, small organic molecule, and the like, that can bind to a biological target. Probes include, but are not limited to, photoaffinity compounds, antibodies, oligonucleotides, oxazolidinone antibiotics, and the like. Probes can be labeled or unlabeled. As used herein, the phrase"susceptible cell"means any cell in which a photoaffinity probe can bind to a biological target. Susceptible cells include, but are not limited to, bacteria, fungi, and mammalian cells. As used herein, the term"test compound"means any identifiable chemical or molecule, small molecule, peptide, protein, sugar, natural or synthetic, that is suspected to potentially interact with or compete with a probe for cross-linking to a biological target within a cell or from a cell. The present invention is directed to methods of using oxazolidinone photoaffinity probes to elucidate and/or identify biological targets of oxazolidinone antibiotics. The present invention is also directed to in vitro assays for determining whether a particular test compound is able to interact with a biological target of oxazolidinone antibiotics. Such methods allow, inter alia, generation of molecular-based drug discovery approaches for novel antibiotics based on the mechanism of antibacterial activity of oxazolidinone antibiotics. One embodiment of the present invention is directed to methods for identifying a biological target of an oxazolidinone-type antibiotic. A susceptible cell is contacted with a probe, such as an oxazolidinone photoaffinity probe. Susceptible cells of the present invention include, but are not limited to, gram positive bacterial pathogens, including, for example, Staphylococcus aureus ; Staphylococcus epidermidis (A, B, C biotypes); Staphylococcus caseolyticus ; Staphylococcus gallinarum ; Staphylococcus haemolyticus ; Staphylococcus hominis ; Staphylococcus saprophyticus ; Streptococcus agalactiae (group B); Streptococcus mutanslrattus ; Streptococcus pneumonias ; Streptococcus pyogenes (group A); Streptococcus salivarius ; Streptococcus sanguis ; Streptococcus sobrinus ; Actinomyces spps. ; Arthrobacter histidinolovorans ; Corynebacterium diptheriae; Clostridium difficle ; Clostridium spps. ; Enterococcus casseliflavus ; Enterococcus durans ; Enterococcus faecalis ; Enterococcus faecium ; Enterococcus gallinarum ; Erysipelotlirix rhusiopathiae ; Fusobacterium spps. ; Listeria monocytogenes ; Prevotella spps. ; Propionibacterium acnes ; and Porphyromonas gingivalis. Susceptible cells also include, but are not limited to, gram negative bacterial pathogens, including, for example, Acinetobacter calcoaceticus ; Acinetobacter haemolyticus ; Aeromonas hydrophila ; Bordetella pertussis ; Bordetella parapertussis ; Bordetella bronchiseptica ; Bacteroides fragilis ; Bartonella bacilliformis ; Brucella abortus ; Brucella melitensis ; Campylobacter fetus ; Cafnpylobacter jejuni ; Chlamydia pneumoniae ; Chlainydiapsittaci ; Chlamydia trachomatis ; Citrobacterfreundii ; Coxiella burnetti ; Edwardsiella tarda ; Edwardsiella hoshinae ; Enterobacter aerogenes, Enterobacter cloacae (groups A and B); Escherichia coli (to include all pathogenic subtypes) Ehrlicia spps. ; Francisella tularensis ; Haemophilus actinomycetemocomitans; Haemophilus ducreyi; Haemophilus haemolyticus; Haemophilus influenzas ; Haemophilus parahaemolyticus ; Haemophilus paraitifluenzae ; Hafnia alvei ; Helicobacter pylori ; Kingella kingae ; Klebsiella oxytoca ; Klebsiella pneunorziae ; Legionella pneumophila ; Legionella spps. ; Morganella spps. ; Moraxella cattarhalis ; Neisseria gonorrhoeae ; Neisseria ntenifzgitidis ; Plesiofnonas shigelloides ; Proteus mirabilis ; Proteus penneri ; Providencia spps. ; Pseudomonas aeruginosa ; Pseudomonas species ; Rickettsia prowazekii ; Rickettsia rickettsii ; Rickettsia tsutsugamushi ; Rochalimaea spps. ; Salmonella subgroup 1 serotypes (to include S. paratyphi and S. typhi) ; Salmonella subgroups 2,3a, 3b, 4, and 5; Serratia marcesans ; Serratia spps. ; Shigella boydii ; Shigella flexneri ; Shigella dysenteriae ; Shigella sonnei ; Yersinia enterocolitica ; Yersinia pestis ; Yersinia pseudotuberculosis ; Vibrio cholerae ; Vibrio vulnificus ; and Vibrio parahaemolyticus. Susceptible cells also include, but are ; not limited to, Mycobacterial species, including, for example, Mycobacterium tuberculosis ; Mycobacterium aviurn ; and other Mycobacterium spps. Susceptible cells also include, but are not limited to, Mycoplasmas (or pleuropneumonia-like organisms), including, for example, Mycoplasme genitalium ; Mycoplasma pneumoniae ; and other Mycoplasma spps. Susceptible cells also include, but are not limited to, Treponemataceae (spiral organisms) including, for example, Borrelia burgdorferi ; other Borrelia species ; Leptospira spps. ; Treponema pallidum. Susceptible cells also include, but are not limited to, mammalian cells. After a susceptible cell is contacted with a photoaffinity probe, the photoaffinity probe is exposed to light, preferably ultraviolet light, in order to form a complex between the photoaffinity probe and the biological target, e. g. cross-link the photoaffinity probe to at least one biological target within the susceptible cell. The complex formed between the photoaffinity probe and the biological target is detected by standard methodology. Preferably, the photoaffinity probe is detectably labeled. Detectable labels include, but are not limited to, enzymatic, fluorescent, chemiluminescent, or radioactive labels, many of which are commercially available. Preferred radioactive labels include, but are not limited to, 3H, 35S, and l25I. The complex between the photoaffinity probe and the biological target is detected by any number of well known detection methods including, for example, autoradiography, enzymatic activity detection, chemical shifts/measurement, fluorescence intensity, ELISA with anti-photoaffinity probe antibodies, and the like, depending upon the particular detectable label that is used. A plurality of photoaffinity probes can also be used at the same time. Applicants have identified several biological targets of oxazolidinone compounds by the methods described above, including, 23S RNA, tRNA, LepA and L27. Another embodiment of the invention is directed to methods of identifying compounds that inhibit binding of a probe to a biological target thereof. Such methods can be used, for example, to identify antimicrobial compounds having a mechanism of action similar to oxazolidinones. A biological target is contacted with a probe, such as an oxazolidinone compound, preferably in vitro. Preferably, the probe is linezolid or eperezolid, or a derivative thereof. The biological target is ribosomal RNA, tRNA, LepA protein, L27 ribosomal protein, or any combination thereof. The biological target is also contacted with a test compound. The amount of binding between the probe and the biological target in the presence and absence of the test compound is compared. A decrease in the amount of binding between the probe and the biological target in the presence of the test compound indicates that the test compound inhibits binding of the probe to the biological target. In some embodiments of the invention, the biological target is bound to a solid phase including, but not limited to, controlled pore glass, a microtiter plate, a column, a scintillation proximity bead, sepharose, polyacrylamide, and the like. Thus, for example, LepA from a susceptible source, or a biologically active fragment of LepA, is attached to scintillation proximity beads (SPA beads), for example, by antibody attached to the beads and directed against an antibody that recognizes the LepA peptide sequence. The test target can also be attached by other standard means such as His-copper, strep-avidin, etc. Microtiter plates containing the SPA beads are then incubated with or without additional targets (as described herein) with a labeled reference probe such as 3H-eperezolid. Test compounds are evaluated for their ability to reduce binding of the labeled probe to the target or collection of targets for the oxazolidinone antibiotics. Compounds able to recognize the same site (s) on the target (s) can have useful antibiotic or antimicrobial activity. Similarly the other targets described herein (e. g. ribosomal RNA, tRNA or L27) can be attached first to the SPA beads and the assay can be constructed and conducted in the same fashion. Unknown compounds that reduce the binding of the labeled probe (e. g. in this example 3H-eperezolid) in a manner similar to unlabeled probe (e. g., in this example eperezolid) can have useful antibiotic or antimicrobial activity. In some embodiments of the invention, the biological target is 23S ribosomal RNA or a fragment thereof. Preferably, the fragment of the 23S RNA comprises the central peptidyl transferase loop. Fragments of 23S RNA can be from about 10 nucleotides to about 1000 nucleotides, more preferably from about 25 nucleotides to about 750 nucleotides, more preferably from about 50 nucleotides to about 500 nucleotides, and more preferably from about 100 nucleotides to about 250 nucleotides in length. Preferably, the fragments comprise contiguous nucleotides from within the nucleotide sequence for the 23S ribosomal RNA. RNA comprising the central peptidyl transferase region and the contacts identified by these techniques include analogous 23S RNA regions, with their respective sequences, that are isolated from any of the organisms recited above. 23S ribosomal RNA can be isolated by the methods described above, or can be isolated or constructed by standard methodology. The nucleotide sequence of S. aureus 23S RNA is described in, for example, Ludwig et al., Syst. Appl. Microbiol., 1992, 15, 487-501 and Brosius et al., Proc. Natl. Acad. Sci. USA, 1980,77,201-4, each of which is incorporated herein by reference in its entirety. 23S RNA can be isolated as described in, for example, Moazed et al., J. Mol. Biol., 1986,187,399-416, which is incorporated herein by reference in its entirety. In some embodiments of the invention, the biological target is a tRNA molecule. Preferably, the tRNA is tRNAflet. The tRNA can be isolated by the methods described above, or can be isolated from cells, such as E. coli, or constructed by standard methodology. The nucleotide sequence and isolation of fmet tRNA is described in, for example, Seong et al., Proc. Natl. Acad. Sci. USA, 1987,84,334-8, which is incorporated herein by reference in its entirety. In some embodiments of the invention, the biological target is LepA protein, or a fragment thereof. Lep A is also known as the protein product of the YqeQ gene. The amino acid sequence of LepA (SEQ ID NO : 1) is shown below. 1 NKRYARSVTR FNGFRKRTMY YNQIKRVRLK YEAKDGNTYT FHLIDTPGHV 51 DFTYEVSRSL AACEGAILW DAAQGIEAQT LANVYLALDN ELELLPVINK 101 IDLPAAEPER VKQEIEDMIG LDQDDVVLAS AKSNIGIEEI LEKIVEVVPA 151 PDGDPEAPLK ALIFDSEYDP YRGVISSIRI VDGVVKAGDK IRMMATGKEF 201 EYtEVGINTP KQLPVDELTV GDVGYIIASI KNVDDSRVGD TITLASRPAS 251 EPLQGYKKMN PMVYCGLFPI DNKNYNDLRE ALEKLQLNDA SLEFEPESSQ 301 ALGFGYRTGF LGMLHMEIIQ ERIEREFGIE LIATAPSVIY QCVLRDGSEV 351 TVDNPAQMPD RODKIDKIFEP YVRATMMVPN DYVGAVMELC QRKRGQFINM 401 DYLDDIRVNI VYELPLAEW FDFFDQLKSN TKGYASFDYE FIENKESNLV 451 KMDILLNGDK VDALSFIVHR DFAYERGKAL VEKLKTLIPR QQFEVPVQAA 501 IGQKIVARTN IKSMGKNvLA KCYGGDISRK RKLLEKQKAG KAKMKKVGNV 551 EIPQDAFLAV LKMDDE Fragments of LepA can be from about 10 amino acids to about 550 amino acids, more preferably from about 25 amino acids to about 500 amino acids, more preferably from about 50 amino acids to about 400 amino acids, more preferably from about 100 amino acids to about 300 amino acids, and more preferably from about 150 amino acids to about 250 amino acids in length. Preferably, the fragments comprise contiguous amino acids from within the amino acid sequence for LepA. LepA can be isolated by the methods described above, or can be isolated or produced by standard methodology, and can be isolated from any of the organisms recited above. LepA can be isolated as described in, for example, March et al., J. Biol. Chez., 1985,260,7206-13, which is incorporated herein by reference in its entirety. In some embodiments of the invention, the biological target is L27, a 11 kDa ribosomal protein, or a fragment thereof. In S. aureus, L27 comprises the following representative amino acid sequence: VRCIPMLKLNLQFFASKKGVSSTKNGRDSESKRLGAKRADGQFVTGGSI LYRQRGTKIYPGENVGRGGDDTLFAKIDGVKFERKGRDKKQVSVYAVAE (SEQ ID NO : 2). In Bacillus subtilis, L27 comprises the following representative amino acid sequence: MLRLDLQFFASKKGVGSTKNGRDSEAKRLGAKRADGQFVTGGSILYRQRGTKIYPGEN VGRGGDDTLFAKIDGTVKFERFGRDRKKVSVY PVAQ (SEQ ID NO : 3). In E. coli, L27 comprises the following representative amino acid sequence: MAHKKAGGSTRNGRDSEAKR LGVKRFGGESVLAGSIIVRQRGTKFHAGANVGCGRDHTLFAKADGKVKFEVKGPKN RKFISIEAE (SEQ ID NO : 4). In Haemophilus influenzae, L27 comprises the following representative amino acid sequence: MATKKAGGSTRNGRDSEAKRLGVKRFGGESVLAG SIIVRQRGTKFHAGNNVGMGRDHTLFATADGKVKFEVKGEKSRKYVVIVTE (SEQ ID NO : 5). A representative reference describing L27 is Chen et al., FEBS Lett., 1975,59,96-99, which is incorporated herein by reference in its entirety. Fragments of L27 can be from about 10 amino acids to about 90 amino acids, more preferably from about 15 amino acids to about 75 amino acids, more preferably from about 20 amino acids to about 50 amino acids, more preferably from about 25 amino acids to about 40 amino acids, and more preferably from about 30 amino acids to about 35 amino acids in length. Preferably, the fragments comprise contiguous amino acids from within the amino acid sequence for L27. L27 can be isolated by the methods described above, or can be isolated or produced by standard methodology, and can be isolated from any of the organisms recited-above. In some embodiments of the invention, a probe is contacted with a plurality of different biological targets including any combination of the biological targets described above. The biological target is also contacted with a test compound. The amount of binding between the probe and the biological target in the presence and absence of the test compound is compared. Binding can be measured either quantitatively or qualitatively by numerous methods known to those skilled in the art. A decrease in the amount of binding between the probe and the biological target in the presence of the test compound indicates that the test compound inhibits binding of the probe to the biological target. A plurality of test compounds can also be screened at the same time. In some embodiments of the invention, the test compounds can be further tested using mammalian cells. Those test compounds that are able to inhibit binding of a probe to a biological target in non-mammalian cells (e. g., bacterial, fungi, etc.) but which are not able to inhibit or insignificantly binding of the probe to a biological target in a mammalian cell can be ideal candidates for treatment of mammals. In these circumstances, the test compound would have activity against a microbe or bacteria while having very little, if any, effect on host mammalian cells. The methods described herein are useful for, inter alia, the molecular description of the nature of the toxicity of antibiotic compounds in eukaryotic cells. In this particular case, the sensitive eukaryotic cells or organelles are incubated and treated as defined above for bacterial cells and the relevant targets are identified. This allows the definition of screens, assays, and structure-based design as discussed below for the discovery of active antibiotics and when used as a negative selection technique allows for optimization of new antibacterial or other therapeutic agents. The photoaffinity probes that can be used in any of the methods described herein are shown below and include, but are not limited to, photoaffinity probes comprising Formula I, Formula II, Formula m, Formula IV, Formula V, or Formula VI, or any mixture thereof. The preferred configuration at C-5 is (S). It will be appreciated by those skilled in the art that compounds of the present can have additional chiral centers and be isolated in optically active or racemic form. The present invention encompasses any racemic, optically-active (such as enantiomers, diastereomers), tautomeric, or stereoisomeric form, or mixture thereof, of a compound of the invention. Preferred compounds of this invention have one radioactive element which is either 3H (T3), 35S, or l25I. It is understood, however, that the Formulas include all isotopic forms of the compounds depicted. In some embodiments of the invention, photoaffinity probes comprise Formula I, shown below. EMI11.1 Formula I wherein X and Y are, independently, F, H or CH3 in a variety of substitution patterns. Preferred compounds have one fluorine and one H. Rl is H, F or I. R2 is H, F or OH. R16 is H or F. Rl7 is H or F. R3 is H or Cl-C8 alkyl. L is a bond or-OCH2C (=O). Q is EMI11.2 wherein R4 is H, CH3, CH2CH3 or cyclopropyl. Z is O or S. Compounds comprising Formula I also include pharmaceutically acceptable salts thereof. Preferred compounds comprising Formula I have the following substituents: X is F, Y is H, R3 is H, and R4 is CH3. More preferably, compounds of Formula I include, but are not limited to, 2- [4- [4- [ (5S)-5- [ (Acetylamino) methyl]-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-1-piperazinyl]- 2-oxoethyl-4-azido-2-hydroxy-5-iodo-l25I-benzoate, N-[[(5S)-3-[4-[4-(4-Azido-2-hydroxy-5iodo-125I-benzoyl)-1-piperazinyl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl] acetamide, 2- [4- [4- [ (5S)-5- [ (Acetylamino) methyl]-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-l- piperazinyl]-2-oxoethyl 4-azido-3-iodo-125I-benzoate, and N-[[(5S)-3-[4-[4-(4-Azido-3-iodo-125I benzoyl)-1-piperazinyl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl] methyl] acetamide. In other embodiments of the invention, photoaffinity probes comprise Formula II, shown below. EMI12.1 Formula II wherein X and Y are, independently, F, H or CH3 in a variety of substitution patterns. Preferred compounds have one fluorine and one H. R1 is H, F or I. R2 is H, F or OH. R16 is H or F. R17 is H or F. Q is EMI12.2 wherein R4 is H, CH3, CH2CH3 or cyclopropyl. Z is O or S. Compounds comprising Formula II also include pharmaceutically acceptable salts thereof.. Preferred compounds comprising Formula I have the following substituents: X is F, Y is H, and R4 is CH3. More preferably, compounds of Formula II include, but are not limited to, N-[[(5S)-3-(4'-Azido-2-fluoro[1,1'-biphenyl]-4-yl)-2-oxo-5-oxazolidinyl]methyl]-T3-acetamide, N-[[(5S)-3-(4'-Azido-2-fluoro-3'-iodo[1,1'-biphenyl]-4-yl)-2-oxo-5-oxazolidinyl] methyl]-T3acetamide, N-[[(5S)-3-(4'-Azido-2-fluoro-3'-iodo[1,1'-biphenyl]-4-yl)-2-oxo-5oxazolidinyl] methyl] ethane-35S-thioamide, and N-[[(5S)-3-(4'-Azido-2-fluoro-3'-iodo-125I-[1,1' biphenyl]-4-yl)-2-oxo-5-oxazolidinyl] methyl] acetamide. In other embodiments of the invention, photoaffinity probes comprise Formula m, shown below. EMI12.3 Formula III wherein X and Y are, independently, F, H or CH3 in a variety of substitution patterns. Preferred compounds have one fluorine and one H. R5 is EMI13.1 wherein R6 is H, N3, halogen, NH2, OH, SH, Cl-C4 alkylamino, C1-C4 dialkylamino, Cl-C4 alkyl, nitrile, carboxamide, C1-C4 alkoxy, Cl-C4 alkylthio, or C1-C4 alkoxycarbonyl. P is EMI13.2 wherein Z is O or S. R7 is EMI13.3 wherein R1 is H, F or 1. R2 is H, F or OH. R16 is H or F. R17 is H or F. Compounds comprising Formula III also include pharmaceutically acceptable salts thereof. Preferred compounds comprising Formula in have the following substituents: X is F, Y is H, and R6 is H. More preferably, compounds of Formula m include, but are not limited to, (2E)-3-(4-azido-3-iodo-125I-phenyl)-N-[[(5S)-3-[3-fluoro-4-(4-pyridinyl) phenyl]-2-oxo-5oxazolidinyl] methyl]-2-propenamide, 4-azido-N- [ [ (5S)-3- [3-fluoro-4- (4-pyridinyl) phenyl]-2oxo-5-oxazolidinyl]methyl]-2-hydroxy-5-iodo-125I-benzamide, and N-(4-azidophenyl)-N'-[[(5S) 3- [3-fluoro-4- (4-pyridinyl) phenyl]-2-oxo-5-oxazolidinyl] methyl]-35S-thiourea. In other embodiments of the invention, the photoaffinity probes comprise Formula IV shown below. EMI14.1 Formula IV wherein X and Y are, independently, F, H or CH3 ; R8 is H, F or 1 ; R9 is H, F or OH; R18 is H or F; R19 is H or F; Rlo is H or C1-C8 alkyl ; L is a bond or-OCH2C (=O) ; and Q is EMI14.2 wherein Rll is H, CH3, CH2CH3 or cyclopropyl ; and Z is O or S; or a pharmaceutically acceptable salt thereof. In other embodiments of the invention, the photoaffinity probes comprise Formula V shown below. EMI14.3 Formula V wherein X and Y are, independently, F, H or CH3 ; R12 is N3 or EMI15.1 whereinR8isH, ForI ; R9 is H, F or OH; R18 is H or F; R19 is H or F ; and Q is EMI15.2 wherein Rll is H, CH3, CH2CH3 or cyclopropyl ; and Z is O or S; or a pharmaceutically acceptable salt thereof. In other embodiments of the invention, the photoaffinity probes comprise Formula VI shown below. EMI15.3 Formula VI wherein X and Y are, independently, F, H or CH3 ; R13 is EMI15.4 wherein R14 is H, N3, halogen, NH2, OH, SH, Cl-C4 alkylamino, C1-C4 dialkylamino, C1-C4 alkyl, nitrile, carboxamide, C1-C4 alkoxy, Ci-C4 alkylthio, or C1-C4 alkoxycarbonyl; and P is EMI16.1 wherein: Z is O or S; and R'5 is EMI16.2 wherein R 8is H, F or I ; and R9 is H, F or OH ; Rl8isHorF ; andRl9isHorF ; or a pharmaceutically acceptable salt thereof. Methods for preparing the photoaffinity probes described in Formulas I, II, m, IV, V, and VI are depicted in the following synthesis schemes. It will be apparent to those skilled in the art that the described synthetic procedures are merely representative in nature and that alternative procedures are feasible and may be preferred in some cases. Non-radioactive compounds of Formulas I and IV are prepared by the methods described in Schemes A and B. As shown in Scheme A, coupling of a benzoic acid moiety (Ai) with an appropriate hydroxyacetyl piperazine fragment (A2) leads to compounds A3 of Formula I where L is-OCH2C (=O). Coupling can be accomplished with 1- [3- (dimethylamino) propyl]-3ethylcarbodiimide hydrochloride or any other reagents familiar to ones skilled in the art. Appropriate benzoic acid fragments can be made by procedures known in the literature. (Dupuis, Can. J. Chez., 1987,65,2450-2453; Shu, J. Labelled Compounds and Radiopliarmaceuticals, 1996,38,227-237, each of which is incorporated herein by reference in its entirety). Appropriate hydroxyacetyl piperazine fragments can also be made by methods known in the literature (Barbachyn, U. S. Patent No. 5,547,950; Barbachyn, U. S. Patent No. 5,990,136; and Snyder, International Publication WO 00/10566-A1, each of which is incorporated herein by reference in its entirety). Methods for incorporation of 125I into compounds A3 are shown in Schemes C and D. Scheme A can also be used where the compounds of A1 and A3 have R16 and R17 substituents ortho to the acid substituent (as in Formulas I and IV). Scheme A: EMI17.1 Non-radioactive compounds of Formulas I and IV where L is a bond are prepared by the synthetic sequence shown in Scheme B. An appropriate benzoic acid fragment (A1 of Scheme A) is coupled with an appropriate piperazine (B2) using 1, 1-carbonyldiimidazole in tetrahydrofuran to give the desired compound (B3). Other coupling methods known to those skilled in the art are also possible. The piperazine fragment is made by methods known in the literature (Hutchinson, U. S. Patent No. 5,700,799, which is incorporated herein by reference in its entirety; Barbachyn, U. S. Patent No. 5,990,136; and Snyder, International Publication WO 00/10566-A1). Methods for incorporation of l25I into compounds B3 are shown in Schemes C and D. Scheme B can also be used where the compound of B3 has R16 and R17 substituents ortho to the amide substituent (as in Formulas I and IV). Scheme B: EMI17.2 B2 B3 Radioactive iodine is introduced into the compounds of Formulas I and IV by the methods shown in Schemes C and D. Compounds C2 of Formula I (where R1 is OH and R2 is 125 1) are prepared by reaction of compounds Ci (prepared according to the methods of Schemes A and B) with NaI and chloramine-T. Scheme C: EMI18.1 C1 C2 Alternatively, compounds D3 of Formulas I and IV (where R1 is H and R2 is 125p are prepared as shown in Scheme D. Reaction of compounds D1 (prepared by the methods shown in Schemes A and B) with hexamethylditin affords the stannanes D2. Reaction of D2 with Nal25I and chloramine-T leads to D3. Scheme D: EMI18.2 Non-radioactive compounds of Formulas II and V are prepared by the method shown in Scheme E. The appropriate biphenyl nitro fragment (El) is reduced in the presence of hydrogen gas and a palladium catalyst to give the appropriate biphenyl aniline fragment (E2). Other reduction methods familiar to those skilled in the art may also be used. Conversion to the azido moiety (E3) can be accomplished via displacement of the appropriate diazonium salt with sodium azide using conditions familiar to those skilled in the art. The appropriate nitro fragments (El) can be prepared by methods known in the literature (Barbachyn, U. S. Patent No. 5,654,435, which is incorporated herein by reference in its entirety; Barbachyn U. S. Patent No. 5,990,136; and Synder, International Publication WO 00/10566-A1) or by other methods familiar to those skilled in the art. Introduction of radioactive elements into compounds of Formulas II and V are depicted in Schemes F, G, and H. Scheme E can also be used where the compounds of El, E2, and E3 have R16 and R17 or R18 and Rl9 substituents in the ortho position (as in Formulas It and V). Scheme E: EMI19.1 E1 E2 E3 Scheme F shows the procedure for incorporation of tritium into compounds of Formulas II and V where Q is oxazolidinone, Z is O, and R4 is CH3. Reaction of Pi (prepared according to Scheme E) with 6N HC1 and methanol affords the free amine F2. Reaction of F2 with tritiated sodium acetate and a coupling reagent affords the tritiated acetamide F3. Suitable coupling reagents include O-benzotriazol-1-yl-N, N, N', N', tetramethyluronium hexafluorophosphate and 0- (7-azabenzotriazol-1-yl)-N, N, N', N'-tetramethyluronium hexafluorophosphate. Other acceptable coupling reagents are known by those skilled in the art. Alternatively, tritiated acetic anhydride and a suitable base can be used in place of tritiated sodium acetate and a coupling reagent. Incorporation of tritium into compounds of Formulas II and V where Q is isoxazoline is carried out in similar fashion. Scheme F can also be used where the compounds of Fl, F2, and F3 have R16 and R17 or R'8 and R'9 substituents in the ortho position (as in Formulas II and V). Scheme F: EMI19.2 EMI19.3 Scheme G shows the method for incorporation of 35S into compounds of Formulas II and V where Q is oxazolidinone, Z is S, and R4 is CH3. Reaction of F2 (from Scheme F) with ethyl 35S-dithioacetate affords the 35S-thioacetamide, G2. Incorporation of 35S into compounds of Formulas II and V where Q is isoxazoline is carried out in similar fashion. Scheme G can also be used where the compound of G2 has R16 and R17 or R'8 and Rl9 substituents in the ortho position (as in Formulas lI and V). Scheme G EMI20.1 Radioactive iodine can be introduced into compounds of Formulas II and V by the method shown in Scheme H. Reaction of H1 (prepared according to the route shown in Scheme E) with hexamethylditin affords the organostannane H2. Reaction of H2 with NaI and chloramine-T affords the radioiodinated compound H3. Scheme H: EMI20.2 H1 H2 H3 Compounds of Formula V where R12 is N3 are made according to the procedures described in U. S. Patent No. 5,910,504, Example 17, which is incorporated herein by reference in its entirety. Scheme I illustrates a synthetic method for the preparation of non-radioactive compounds of Formulas in and VI where P is oxazolidinone, Z is O, and R7 is optionally substituted azidophenyl or azidocinnamoyl. Refluxing an appropriate acetamide fragment (I1) in methanolic hydrochloric acid affords the free amine I2. The acetamide fragments (il) are prepared by methods known in the literature (Barbachyn, U. S. Patent No. 5,565,571, which is incorporated herein by reference in its entirety; Barbachyn, U. S. Patent No. 5,990,136; and Synder, International Publication WO 00/10566-A1). Coupling of I2 with an appropriate benzoic acid fragment (I3, n = 0) or cinnamic acid fragment (I3, n = 1) leads to the amide I4. Coupling can be accomplished with EDC or other reagents familiar to ones skilled in the art. Appropriate benzoic acid fragments 3, n = 0) are prepared by the same method used to prepare A1 of Scheme A. Appropriate cinnamic acid fragments (I3, n = 1) can be prepared by coupling of an appropriate benzaldehyde with Wittig-Horner reagents. Benzaldehyde fragments can be prepared by procedures known in the literature (Shu, J. Labelled Compounds and Radiopharmaceuticals, 1996, 38, 227-237) or by other methods familiar to those skilled in the art. Compounds of Formulas III and VI where P is isoxazoline or isoxazolinone are made by similar methods. Scheme I can also be used where the compounds of Is and I4 have R16 and R17 or R18 and Rl9 substituents in the ortho position (as in Formulas III and VI). Scheme I : EMI21.1 Introduction of 125I into compounds of Formulas m and VI where P is oxazolidinone, Z is O, and R7 is optionally substituted azidophenyl or azidocinnamoyl is accomplished by the method shown in Scheme J. Reaction of I4 (from Scheme I, where Ru ils H and R2 is OH) with NaI and chloramine-T affords the radioiodinated compound J2. Introduction of 125I into compounds of Formulas III and VI where P is isoxazoline or isoxazolinone is carried out by similar methods. Scheme J: EMI22.1 Alternatively, introduction of l25I into compounds of Formulas in and VI where P is oxazolidinone, Z is O, and R7 is optionally substituted azidophenyl or azidocinnamoyl is carried out by the method shown in Scheme K. Reaction of I4 (from Scheme I, where R1 is I and R2 is H) with hexamethylditin affords the organostannane K2. Reaction of K2 with NaI and chloramine-T affords the radioiodinated compound K3. Radioiodination of compounds of Formulas DI and VI where P is isoxazoline or isoxazolinone is carried out in similar fashion. Scheme K : EMI22.2 Scheme L illustrates a synthetic method for the preparation of radioactive compounds of Formulas m and VI where P is oxazolidinone, Z is 35S, and R7 is optionally substituted azidoaniline. An appropriate 35S-isothiocyanate L2 is reacted with the appropriate aminomethyl fragment Iz (Scheme I) in refluxing THF to give the desired 35S-thiourea, (L3). The required 35Sisothiocyanate L2 is prepared by reaction of an appropriate aniline with 35S-thiophosgene. Introduction of 35S into compounds of Formulas III and VI where P is isoxazoline or isoxazolinone is carried out in similar fashion. Scheme L can also be used where the compounds of L2 and L3 have R16 and R17 or R18 and Rl9 substituents in the ortho position (as in Formulas III and VI). Scheme L: EMI23.1 The invention is further illustrated by way of the following examples which are intended to elucidate the invention. These examples are not intended, nor are they to be construed, as limiting the scope of the disclosure. EXAMPLES Example 1: Synthesis 2- [4- [4- [ (5S)-5- [ (Acetylamino) methyl]-2-oxo-3-oxazolidinyll-2-fluorophenyl]-l- piperazinyl]-2-oxoethyl 4-azido-2-hydroxy-5-iodo-lzsI-benzoate (Compound C2 of Scheme C where L is-CH2C (=O), X is F, Y is H, Q is oxazolidinone, Z is O and R4 is CH3) is prepared as follows. EMI23.2 Step 1. To a stirred solution of (S)-N-[[3-[3-fluoro-4[4-(hydroxyacetyl)-1-piperazinyl] phenyl]-2-oxo-5-oxazolidinyl] methyl] acetamide (515.8 mg, 1.31 mmol) in dimethylformamide (10 ml) and pyridine (1 ml) is added 1- [3- (dimethylamino) propyl]-3-ethylcarbodiimide hydrochloride (509.9 mg, 2.66 mmol) followed by 4-azidosalicylic acid (Dupuis, Can. J. Chem., 1987,65,2450-2453) and a catalytic amount of 4-dimethylaminopyridine. The reaction mixture is stirred at room temperature for 72 hours then concentrated. The residue is diluted with CH2C12 (100 ml) and is washed successively with H2O (2 x 30 ml), 1 N HC1 (2 x 30 ml), saturated NaHCO3 (1 x 30 ml), dried (MgS04), filtered and concentrated. The residue is dissolved in CH3OH/CH2C12, absorbed onto silica gel and is purified on a Biotage 40S column with a SIM using 2.5 % CH30H in CH2C12 as the eluent to give 186. 5 mg (0.33 mmol, 25 %) of the benzoate ester. mp 177-178 C (dec). lH-NMR (DMSO) 6 : 10.4,8.24,7.87,7.53,7.17,7.09,6.76,6.70, 5.17,4.71,4.09,3.71,3.60,3.40,3.02,2.96,1.83. Step 2. All reagents are prepared in 0.1 N NaP04 buffer, pH 7.4 unless otherwise specified. Buffer (70 gel), chloramine-T (70 gl of a 1 mM stock solution), and the azido phenol of Step 1 (10 tl of a 50, uM stock solution in DMSO) are added to a 1.5 ml glass reaction vial. A rubber septum cap is crimped onto the reaction vial and a solution of l25I2 in sodium hydroxide (10 gel containing 1 mCi (Amersham &num;IMS 30) is added. The reaction is gently vortexed in the dark for 2 hours at room temperature then quenched with 10% solution of sodium bisulfite (100 gel). The quenched reaction is diluted with buffer (800 gel) and transferred from the reaction vial with a 1 ml tuberculin syringe fitted with an 18 gauge needle. The reaction volume (1 ml) is loaded onto a preconditioned C18 sep-pak cartridge (Millipore Corporation) and the unincorporated 125 I2 is washed from the C 18 resin with HPLC grade water containing 0.1 % trifluoroacetic acid (20 ml). Product is eluted using of 80% CH3CN/0. 1 TFA (3 ml). The typical yield of iodinated product is approximately 30% of the total 125 I2 added to the reaction. Example 2: Synthesis N-[[(5S)-3-[4-[4-(4-Azido-2-hydroxy-5-iodo-125I-benzoyl)-1-piperazinyl]-3 fluorophenyl]-2-oxo-5-oxazolidinyl] methyl] acetamide (Compound C2 of Scheme C where L is a bond, X is F, Y is H, Q is oxazolidinone, Z is O and R4 is CH3) is prepared as follows. EMI24.1 Step 1. To a stirred suspension of (S)-N-[[3-[4-[3-fluoro-4-(1-piperazinyl)] phenyl]-2oxo-5-oxazolidinyl] methyl]-acetamide (498.0 mg, 1.3 mmol) in CH2C12 (10 ml) is added diisopropylethylamine (0.70 ml, 4.0 mmol) followed by 4-azidosalicoyl chloride (342.6 mg, 1.7 mmol) in CH2C12 (7 ml). The reaction mixture is stirred at room temperature for 18 hours and then is partitioned between CH2C12 (50 ml) and H20 (10 ml). The phases are separated. The organic layer is washed with H20 (10 ml), dried (MgSO4), filtered and concentrated. The residue is dissolved in CH3OH/CH2C12, absorbed onto silica gel and is purified on a Biotage 40S column with a SIM using 3% CH30H in CH2C12 as the eluent to afford 412.3 mg (0.83 mmol, 62%) of the desired benzamide as a tan solid. mp 188-189 C (dec). lH-NMR (DMSO) 8 : 10.2,8.24, 7.51,7.22,7.16,7.07,6.64,6.58,4.70,4.07,3.70,3.36,2.96,1.83. Step 2. Starting with the phenol prepared in Step 1, 125 1 is introduced according to the procedure described in Step 2 of example 1. Example 3: Synthesis 2- [4- [4- [ (5S)-5- [ (Acetylamino) methyl]-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-l- piperazinyl]-2-oxoethyl 4-azido-3-iodo-l25I-benzoate (Compound D3 of Scheme D where L is CH2C (=O), X is F, Y is H, Q is oxazolidinone, Z is O and R4 is CH3) EMI25.1 Step 1. To a stirred solution of 4-azido-3-iodobenzoic acid (103.8 mg, 0.36 mmol, (Shu, J. of Labelled Conzpoufzds ayad Radiopharmaceuticals, 1996, 38, 227-237)) in dry THF (2.0 ml) is added 1, 1-carbonyldiimidazole (58.2 mg, 0.36 mmol). The reaction mixture is stirred at room temperature for 1 hour, then (S)-N-[[3-[3-fluoro-4[4-(hydroxyacetyl)-1-piperazinyl] phenyl]-2oxo-5-oxazolidinyl] methyl] acetamide (141.9 mg, 0.36 mmol) is added followed by a catalytic amount of DMAP. The reaction mixture is heated at reflux for 72 hours. The reaction mixture was cooled to room temperature and poured into CH2C12 (30 ml) and washed successively with H20 (15ml), 1 N HC1 (15 ml), saturated aqueous NaHCO3 (15 ml), brine (15 ml), dried (MgS04), filtered and concentrated. The residue is purified on a Biotage 12M column using 2 % CH30H in CH2C12 as the eluent to afford 119.6 mg (0.18 mmol, 50%) of the benzoate ester. mp 137-139 C. 1H-NMR (CDC13) 8 : 8.52,8.14,7.49,7.19,7.07,6.95,6.01,5.00,4.72,4.02,3.81, 3.75,3.62,3.05,1.58. Step 2. To a stirred solution of the iodobenzoate prepared in Step 1 (62.7 mg, 0.094 mmol) and hexamethylditin (46.3 mg, 0.14 mmol) in dry THF (3 ml) is added dichlorobis (triphenylphosphine) palladium (II) (2.0 mg, 0.003 mmol). The reaction mixture is degassed and is heated at reflux for 3 hours. The reaction mixture is cooled and filtered through a pad of celite. The filtrate is absorbed onto silica gel and purified on a Biotage 12M column with SIM using 2 % CH30H in CH2C12 as the eluent to afford 28.6 mg (0.04 mmol, 43 %) of the stannane. lH-NMR (DMSO) o : 8. 25,8.04,8.00,7.48,7.42,7.15,7.10,5.10,4.73,4.09,3.71, 3.60,3.40,3.02,2.96,1.83,0.33. Step 3. To a stirred solution of the stannane prepared in Step 2 in dry acetonitrile is added a solution of 1M aqueous NaI followed by chloramine-T hydrate. After stirring at room temperature for 30 minutes, the reaction mixture is quenched with saturated aqueous Na2S203 and purified to give the radioiodinated material. Example 4: Synthesis N-[[(5S)-3-[4-[4-(4-Azido-3-iodo-125I-benzoyl)-1-piperazinyl]-3-fluorophenyl]-2-oxo-5oxazolidinyl] methyl] acetamide (Compound D3 of Scheme D where L is a bond, X is F, Y is H, Q is oxazolidinone, Z is O and R4 is CH3) EMI26.1 Step 1. To a stirred solution of 4-azido-3-iodobenzoic acid (272.0 mg, 0.94 mmol) in dry THE (4 ml) is added 1, 1-carbonyldiimidazole (152.6 mg, 0.94 mmol). The reaction mixture is stirred at room temperature for 1 hour, then (S)-N- [ [3- [4- [3-fluoro-4- (1-piperazinyl)] phenyl]2-oxo-5-oxazolidinyl] methyl]-acetamide (315.9 mg, 0.94 mmol) is added followed by DMF (2 ml). The reaction mixture is heated at reflux for 18 hours. The reaction mixture is cooled and poured into CH2C12 (40 ml) and successively washed with H20 (20 ml), 1 N HC1 (20 ml), saturated aqueous NaHCO3 (20 ml), brine (20 ml), dried (MgS04), filtered and concentrated. The residue is dissolved in CH2C12, absorbed onto silica gel and is purified on a Biotage 40S column with SIM using 2.5 % CH30H in CH2C12 as the eluent to afford 376.7 mg (0.62 mmol) of the benzamide as a yellow solid. 1H-NMR (DMSO) 8 : 8.24,7.88,7.53,7.47,7.39,7.19,7.08,4.71, 4.08,3.70,3.51,3.40,2.99,1.83. Step 2. To a stirred solution of the iodobenzamide prepared in Step 1 (82.4 mg, 0.13 mmol) and hexamethylditin (71.1 mg 0.22 mmol) in dry THF (6 ml) is added tetrakis (triphenylphosphine) palladium (0). The reaction mixture is degassed and heated at reflux for 12 hours. The cooled reaction mixture is filtered through a plug of celite and the filtrate is absorbed onto silica gel and purified on a Biotage 12M column with SIM using 2 % CH30H in 49% CH2C12 and 49% EtOAC as the eluent to afford 28.2 mg (0.044 mmol, 34 %) of the stannane. 1H-NMR (DMSO) 8 : 8.24,7.50,7.43,7.35,7.18,7.17,4.71,4.08,4.01,3.70,3.40, 2.99,1.83,0.32. Step 3. To a stirred solution of the stannane prepared in Step 2 in dry acetonitrile is added a solution of 1M aqueous NaI followed by chloramine-T hydrate. After stirring at room temperature for 30 minutes, the reaction mixture is quenched with saturated aqueous Na2S203 and purified to give the desired radioiodinated material. Example 5: Synthesis N- [ [ (5S)-3- (4'-Azido-2-fluoro [1, 1'-biphenyl]-4-yl)-2-oxo-5-oxazolidinyl] methyl]-T3- acetamide (Compound F3 of Scheme F where Rlis H, R2 is H, X is F, and Y is H) EMI27.1 Step 1. To a stirred solution of 4-iodonitrobenzene (6.86 g, 27.5 mmol) in dry DMF (230 ml) is added bis (pinacolato) diboron (8.24 g, 32.4 mmol) followed by potassium acetate (8.68 g, 88.5 mmol) and [1, 1'-bis (diphenylphosphino) ferrocene] dichloropalladium (lui) (624.6 mg, 0.76 mmol). The reaction mixture is degassed and heated at 85 C for 2 hours. To the cooled dark reaction mixture is added (S)-N- [ [3- (3-fluoro-4-iodophenyl)-2-oxo-5-oxazolidinyl] methyl] acetamide (5.8 g, 15.3 mmol) followed by 2 N aqueous Na2C03 (143 ml) and [1, 1'-bis (diphenylphosphino) ferrocene] dichloropalladium (II) (312.0 mg, 0.38 mmol). The reaction mixture is degassed and heated at 85 C for 3 hours. The cooled reaction mixture is partitioned between EtOAC (500 ml) and H20 (300 ml). The phases are separated. The aqueous layer is extracted with EtOAC (300 ml). The organic layers are combined and successively washed with H20 (500 ml), brine (500 ml), dried (MgS04), filtered and concentrated. The residue is dissolved in CHsOH/CHzClz, absorbed onto silica gel and is purified on a Biotage 40 M column (2 lots) with SIM using 75 % EtOAC in CH2C12 to 100 % EtOAC as the eluent to afford 3.74 g (10.0 mmol, 65%) of the desired nitrobiphenyl compound. 1H-NMR (DMSO) 6 : 8. 30,7.83,7.68,7.50, 4.78,4.18,3.80,3.44,1.84. Step 2. A mixture of the nitrobiphenyl compound prepared in Step 1 (3.74 g, 10.0 mmol), 10% palladium on carbon in THE (100 ml), CH30H (100 ml) and CH2C12 (100 ml) is hydrogenated under a balloon of hydrogen for 18 hours. The reaction mixture is filtered through a pad of celite and the filtrate is concentrated to afford 2.50 g (7.3 mmol, 73%) of the desired aminobiphenyl. lH-NMR (DMSO) 6 : 8. 26,7.45,7.34,7.23,6.64,5.28,4.73,4.14,3.76,3.42, 1.84. Step 3. To a stirred solution of the aminobiphenyl prepared in Step 2 (508. 93 mg, 1.48 mmol) in CH30H (40 ml) and 1 M HC1 (40 ml), cooled to 0 C is added a 1.2 M aqueous NaN02 solution (1.48 ml, 1.78 mmol). The reaction mixture is stirred at 0 C for 90 minutes, then sulfamic acid (143.5 mg, 1.48 mmol) is added followed by sodium azide (115.4 mg, 1.78 mmol) in H20 (1.5 ml). The reaction mixture is stirred at 0 C for 45 minutes, then diluted with CH2C12 (200 ml). The phases are separated. The aqueous phase is extracted with CH2C12 (75 ml). The combine organic phases are dried (MgS04), filtered and concentrated. The residue is dissolved in CH30H/CH2C12, absorbed onto silica gel and is purified on a Biotage 40S column with SIM using 10% CH30H in CH2C12 as the eluent to afford 262.9 mg (0.71 mmol, 48%) of the desired azidobiphenyl as a pale yellow solid. 1H-NMR (DMSO) 6 : 8.27,7.58,7.42,7.24,4.76,4.16, 3.78,3.43,1.84. Step 4. The azidobiphenyl prepared in Step 3 (102.4 mg, 0.27 mmol) in 6 N HC1 (2 ml) and CH30H (6 ml) is heated at reflux for 18 hours. The CH30H is removed in vacuo and the solid precipitate is isolated by filtration and is washed successively with H20 (10 ml), ether (2 x 15 ml) then dried to afford 82. 1 mg (0.23 mmol, 82%) of the desired amine hydrochloride. 1H NMR (DMSO) 8 : 8.30,7.62,7.42,7.25,4.98,4.25,3.91. Step 5. To a stirring solution of 0.57 mg (6.94 umol, 250 mCi) of tritiated acetic acid sodium salt (American Radiolabeled Chemicals, lot no ARC 990519) in 1 ml of dry DMF and 2.71 mg (21 umol) ofdiisopropylethylamine at room temperature, is added 6.94 umol of 0.45M O-Benzotriazol-1-yl-N, N, N', N'-tetramethyluronium hexafluorophosphate (HBTU) in dry DMF. The solution instantly turned pale yellow and is stirred at room temperature for 10 minutes. The activated [3H] acetic acid sodium salt was then added to a stirring solution of 2.73 mg (7.5 umol) of the amine hydrochloride prepared in Step 4 in 2 ml of dry DMF. The reaction is stirred at room temperature for 4.5 hours, then all solvents are removed by vacuum distillation at room temperature. The crude reaction mixture is purified on a preparative TLC plate (Analtech Silica gel GF, 500 micron, 20 cm x 20 cm plate), eluted with 8% methanol in dichloromethane. The desired band is scrapped. The product is eluted from the silica gel with 20% methanol in dichloromethane and filtered. The filtrate is concentrated under vacuum, and the residue is dissolved in 65.5 ml of methanol to afford 94.4 mCi of the desired tritiated material (1.44 mCi/ml methanol, specific activity 57.37 mCi/mg (57.37 Ci/mmol), radiochemical purity 99.5% by HPLC). Example 6: Synthesis N-[[(SS)-3-(4'-Azido-2-fluoro-3'-iodo [l, 1'-biphenyl]-4-yl)-2-oxo-5- oxazolidinyl] methyl]-T3-acetamide (Compound F3 of Scheme F where Rlis H, R2 is I, X is F, and YisH) EMI29.1 Step 1. To a stirred solution of the aniline prepared in Step 2 of Example 5 (284.9 mg, 0.83 mmol) in acetic acid (3 ml) is added iodine monochloride (134.5 mg, 0.83 mmol) in acetic acid (0.25 ml). The reaction mixture is stirred at room temperature for 1.5 hours. The reaction mixture is partitioned between EtOAc and aqueous Na2S203. The phases are separated. The aqueous phase is extracted with EtOAc (20 ml). The combined organic phases were dried (MgS04), filtered and concentrated. The residue is dissolved in CH30H, absorbed onto silica gel and is purified on a Biotage 40S column with SIM using 10-25 % acetone in CH2C12 as the eluent to afford 48.4 mg (0.10 mmol, 12%) of the desired iodoaniline as a yellow oil. lH-NMR (CH30D) 8 : 7.73,7.52,7.29,6.85,4.81,4.10,3.79,3.53,3.32,1.98. Step 2. To a stirred solution of the iodoaniline prepared in Step 1 (47.2 mg, 0.10 mmol) in CH30H (2 ml) and 1N HC1 (2 ml) cooled to 0 C, is added a solution of NaN02 (8.5 mg, 0.12 mmol) in H2O (1 ml). The yellow reaction mixture is stirred at 0 C for 30 minutes, then a solution of NaN3 (8.0 mg, 0.12 mmol) in H20 (1 ml) is added. The reaction mixture is stirred at 0 C for 1 hour, during which time a yellow precipitate formed. The solid is isolated by filtration and washed with H20 and dried to afford 41.0 mg (0.083 mmol, 83%) of the desired iodoazidobiphenyl as a yellow solid. mp 173-175 C (dec). lH-NMR (DMSO) 8 : 8.27,7.98, 7.60,7.42,4.76,4.16,3.78,3.43,1.84. Step 3. A mixture of 129 mg (0.26 mmol) of the iodoazidobiphenyl prepared in Step 2 (129.0 mg, 0.26 mmol), CH30H (6 ml) and 1 N HC1 (2 ml) are heated at reflux for 48 hours. The cooled reaction mixture is concentrated to afford quantitative yield the desired amine hydrochloride as a tan solid. lH-NMR (CH30D) o : 7.96,7.63,7.46,7.38,7.29,5.04,4.34,3.93, 3.38,1.30. Step 4. To a solution of 5.1 mg (0.05 mmol, 25 mCi) of tritiated acetic anhydride (Amersham Batch B77, isotope &num; 00-0316) is added 2 N PC13 in CH2Cl2 (25 ut). The reaction mixture is left at room temperature for 5 hours with occasional mixing. To this mixture is added a solution of the amine hydrochloride prepared in Step 3 (47.7 mg, 0.104 mmol) in pyridine (0.25 ml) followed by DMAP (4.6 mg). After 30 minutes, the reaction mixture is partitioned between H20 and CH2C12. The phases are separated. The aqueous phase is extracted exhaustively with CH2C12 and then concentrated. The residue is purified on silica gel (4 g) using 20 % acetone in toluene as the eluent to afford 38.2 mg (0.077 mmol, 74 %) of desired tritiated acetamide. Example 7: Synthesis N- [ [ (5S)-3- (4'-Azido-2-fluoro-3'-iodo [1, 1'-biphenyl]-4-yl)-2-oxo-5- oxazolidinyl] methyl] ethane-35S-thioamide (Compound G2 of Scheme G where Rlis H, R2 is I, X isF, andYisH) EMI30.1 Step 1. Methylmagnesium chloride in tetrahydrofuran (THF) is treated with 35S labeled carbon disulfide at 40 C, followed by treatment with ethyl iodide. The reaction is stirred at 60 C for 1.5 hours. After workup with water and ethyl ether, the desired ethyl 35S-dithioacetate is obtained. Step 2. The amine hydrochloride salt prepared in Step 3 of Example 6 and the ethyl [35S] dithioacetate prepared in Step 1 are stirred in methylene chloride, methanol, and triethylamine to give the desired 35S labeled thioamide. Example 8: Synthesis N-[[(5S)-3-(4'-Azido-2-fluoro-3'-iodo-l25I-[1, 1'-biphenyl]-4-yl)-2-oxo-5- oxazolidinyl] methyl] acetamide (Compound H3 of Scheme H where X is F, Y is H, Q is oxazolidinone, Z is O, and R4 is CH3) EMI30.2 Step 1. To a stirred solution of the iodobiphenyl prepared in Step 2 of Example 6 (56.2 mg, 0.11 mmol) and hexamethylditin (73.9 mg, 0.22 mmol) in toluene (5 ml) is added palladium (II) acetate (2.6 mg, 0.011 mmol) followed by triphenylphosphine (6.5 mg, 0.022 mmol). The reaction mixture is degassed and heated at 80 C for 20 hours. The cooled reaction mixture is concentrated to one half the volume, then purified on a Biotage 12S column using 10-20 % acetone in CH2C12 as the eluent to afford 53.5 mg (0.10 mmol, 89%) of the desired stannane. 1H- NMR (CDC13) # : 7.53,7.43,7.30,7.21,6.07,4.83,4.11,3.83,3.73,2.05,0.35. Step 2. To a stirred solution of the stannane prepared in Step 1 in dry CH3CN and pH 7 phosphate buffer is added chloramine-T followed by a solution of 1M aqueous Nazis After 30 minutes, the reaction mixture is quenched with saturated aqueous Na2S203 and purified to give the title compound. Example 9: Synthesis (2E)-3-(4-Azido-3-iodo-125I-phenyl)-N-[[(5S)-3-[3-fluoro-4-(4-pyridinyl)phenyl]-2-oxo5-oxazolidinyl] methyl]-2-propenamide (Compound I4 of Scheme I where Rs is 4-pyridyl, X is F, Y is H, n is 1, Rl is l25I and R2 is H) EMI31.1 Step 1. To a stirred solution of oxalyl chloride (0.10 ml, 1.2 mmol) in CH2C12 (1.5 ml), cooled to-78 C, is added dry DMSO (0.14 ml, 1.97 mmol). After 10 minutes, a solution of 4azido-3-iodobenzyl alcohol (217.0 mg, 0.79 mmol (Shu, J. of Labeled Co7npounds and Radiophannaceuticals, 1996,38,227-237)) in CH2C12 (2.5 ml) is added. After 15 minutes, triethylamine (0.33 ml, 2.37 mmol) is added and the reaction mixture is allowed to warm to room temperature. The reaction mixture is poured into CH2C12 (30 ml) and washed successively with H20 (20 ml), brine (20 ml), dried (MgSO4), filtered and concentrated. The residue is purified on a Biotage 12M column using 10% EtOAC in hexane to afford 195.5 mg (0.72 mmol, 91%) of the desired aldehyde. lH-NMR (CDC13) o : 9.9,8.31,7.93,7.28. Step 2. To a stirred solution of the aldehyde prepared in Step 1 (190.0 mg, 0.69 mmol) in dry THF (1 ml) is added triethylphosphonoacetate (0.15 ml, 0.76 mmol) followed by lithium hydroxide monohydrate (32.1 mg, 0.76 mmol). The reaction mixture is stirred at room temperature for 48 hours. The reaction mixture is poured into CH2C12 (40 ml) and successively washed with H20 (20 ml), brine (20 ml), dried (MgS04), filtered and concentrated. The residue is dissolved in CH2C12, absorbed onto silica gel and purified on a Biotage 40S column with a SIM using 5% EtOAC in hexane as the eluent to afford 165.1 mg (0.48 mmol, 70 %) of the desired ester. mp 93-94 C. lH-NMR (CDC13) o : 7.97,7.56,7.16,6.40,4.29,1.35. Step 3. To a stirred solution of the ester prepared in Step 2 (66.7 mg, 0.19 mmol) in CH30H (2 ml) is added 1 N LiOH (0.19 ml, 0.19 mmol). The reaction mixture is heated at reflux for 12 hours. The cooled reaction mixture is concentrated and used immediately. Step 4. (S)-N- [ [3- [3-fluoro-4- (4-pyridyl) phenyl]-2-oxo-5-oxazolidinyl] methyl] acetamide (1.40 g, 4.25 mmol) in CH30H (62 ml) and 6 N HC1 (31 ml) is heated at reflux for 18 hours. The reaction mixture is concentrated to afford 1.48 g of the amine bis-hydrochloride salt. H-NMR (DMSO) 8 : 8. 98,8.62,8.26,7.75,7.56,7.35,5.76,5.07,4.28,4.30,3.27. Step 5. The amine bis-hydrochloride (from Step 4) (68. 2 mg, 0.19 mmol), the lithium carboxylate prepared in Step 3,1- [3- (dimethylamino) propyl]-3-ethylcarbodiimide hydrochloride (72.8 mg, 0.38 mmol) and 1-hydroxybenzotriazole hydrate (30.8 mg, 0.23 mmol) are dissolved in pyridine (2 ml) and stirred at room temperature for 72 hours. The reaction mixture is concentrated. The residue is dissolved in CH2C12 (40 ml) and washed with H2O (20 ml), brine (20 ml), dried (MgS04), filtered and concentrated. The residue is dissolved in CH30H/CH2C12, absorbed onto silica gel and is purified on a Biotage 12M column with SIM using 2 % CH30H (saturated with NH3) in CH2C12 as the eluent to afford 56.2 mg (0.096 mmol, 51%) of the desired cinnamide. lH-NMR (DMSO) 6 : 8.66,8.48,8.02,7.64,7.49,7.40,7.35,6.70,4.86,4.22,3.84, 3.60. Step 6. To a stirred solution of the iodocinnamide prepared in Step 4 and hexamethylditin in dry THF is added tetrakis (triphenylphosphine) palladium (0). The reaction mixture is degassed and heated at reflux for 12 hours. The cooled reaction mixture is filtered through a plug of celite and the filtrate is absorbed onto silica gel and purified on a Biotage 12M column with SIM to afford the stannane. Step 7. To a stirred solution of the stannane prepared in Step 5 in dry acetonitrile is added a solution of 1M aqueous NaI followed by chloramine-T hydrate. After stirring at room temperature for 30 minutes, the reaction mixture is quenched with saturated aqueous Na2S203 and purified to give the desired radioiodinated material. Example 10: Synthesis 4-Azido-N- [ [ (5S)-3- [3-fluoro-4- (4-pyridinyl) phenyl]-2-oxo-5-oxazolidinyl] methyl]-2 hydroxy-5-iodo-l2sI-benzamide (Compound J2 of Scheme J where Rs is 4-pyridyl, X is F, and Y is H, and n is 0) EMI32.1 Step 1. To a stirred suspension of the amine bis-hydrochloride salt prepared in Step 4 of Example 9 (172.4 mg, 0.48 mmol) in pyridine (4 ml) and CH2C12 (1 ml) is added 4-azidosalicylic acid (128.9 mg 0.72 mmol) followed by added 1- [3- (dimethylamino) propyl]-3-ethylcarbodiimide hydrochloride (184.0 mg, 0.96 mmol) and 1-hydroxybenzotriazole hydrate (77.8 mg, 0.58 mmol). The reaction mixture is stirred at room temperature for 72 hours then concentrated. The residue is dissolved in CH3OH/CH2C12, absorbed onto silica gel and purified on a Biotage 40S column with SIM using EtOAC as the eluent to afford 44.8 mg (0.10 mmol, 21%) of the benzamide as a tan solid. mp 200-202 C (dec). lH-NMR (DMSO) 8 : 12.5,9.1,8.66,7.92,7.70, 7.67,7.61,7.50,7.46,6.70,6.60,4.93,4.25,3.92,3.70. Step 2. Starting with the phenol prepared in Step 1, l25I is introduced according to the procedure described in Step 2 of Example 1. Example 11: Synthesis N- (4-Azidophenyl)-N'- [ [ (SS)-3- [3-fluoro-4- (4-pyridinyl) phenyl]-2-oxo-5-oxazolidinyl] methyl] 35S-thiourea (Compound L3 of Scheme L where Rs is 4-pyridyl, X is F, Y is H, Rl is H and R2 is H) EMI33.1 To a stirred solution of the amine bis-hydrochloride (from Step 4 of Example 9) in dry THF is added Hunig's base followed by 35S-4-azidophenylisothiocyanate in THF. The reaction mixture is heated at reflux for 1 hour. The cooled reaction mixture is cooled and purified to give the desired thiourea. Example 12: Identification Of Biological Targets Bacteria with sensitivity to parent antibiotic (for example S. aureus or other sensitive gram positive or gram negative bacteria) are grown in complete Mueller-Hinton medium to midexponential phase. Representative aliquots of the culture are briefly sedimented in RNase-free tubes (1.5 ml capacity) and then resuspended in fresh Mueller-Hinton medium. Competitor compounds (active or inactive as antibiotics) are added from a stock containing DMSO (total final concentration = 0.2%). The active photoaffinity probe (for example, compounds such as those described in Formulas within; mixture of unlabeled and l25I-labeled, 3H-labeled, or any other suitable radiolabeled or non-radiolabeled, detectable compound) is then added to a final concentration near the minimum inhibitory concentration (MIC) for antibacterial action. This exposure is continued in the dark for 30 minutes at 37 C. The bacteria are then exposed directly to ultraviolet light or briefly sedimented, resuspended in phosphate buffered saline (PBS), and then exposed to ultraviolet light to activate the photoprobe (Stratalinker at energy setting 180,000 microjoules). The labeled cells are then washed with PBS, resuspended in Buffer A (10 mM Tris-HCL (pH 7.6), 30 mM NH4C1, 30 mM MgCl2) and lysed with lysostaphin (5 llg/ml final concentration of lysostaphin for 15 minutes at 37 C). Cell wall and large membrane fragments are then removed by centrifugation at 18,000 x g for 15 minutes. The resulting supernatant is sedimented at 450,000 x g for 60 minutes, yielding a pellet containing cell membrane and ribosomes. The pellet is resuspended in Buffer B (10 mM Tris-HCl (pH 7.6), 0.5 % SDS and 6 mM EDTA), and the RNA is extracted by a standard phenol extraction procedure. RNA extracts are precipitated with ethanol and resuspended in the appropriate buffer for electrophoresis of RNA. Crude pellets are subjected to electrophoresis for proteins. Crosslinking of the labeled photoprobe to, for example, ribosomal RNA (ribosomal RNA of the 23S, 16S, 5S size) or to transfer RNA is detected by RNase H digestion and subsequent primer extension assays, yielding the precise base at which crosslinking occurs. Specific crosslinking events can be validated through the use of biologically active antibacterial compounds, resulting in a reduction in the amount of crosslinking. Additional validation of the crosslinking event (s) is obtained by observing that competitor antibiotics, which are not biologically active (devoid of antibacterial activity), fail to decrease the amount of specific crosslinking to the RNA and/or protein target (s). Using this approach, portions of RNA (23S RNA peptidyltransferase region including A2602, U2506, A2451), tRNA together with the 64 kDa LepA and 11 kDa L27 proteins have been identified as biological targets and can be used in the discovery of unique inhibitors of protein translation based on this mechanism. Example 13: Identification of Antibiotic Compounds The proteins (e. g., the 64 kDa and the 11 kDa proteins, LepA and L27, respectively) and/or RNA components are used either alone or in combination in recognition assays to detect the binding of a representative photoaffinity probe, such as an oxazolidinone photoaffinity probe or equivalent compound, that is labeled by either radioactive or non-radioactive (e. g., enzymatic, chemiluminescent or fluorescent) means. The ability of test compounds to interfere with the interaction is measured. Increased interaction with these sites is/are used as positive selection criteria, whereas interaction with eukaryotic sites is used as a negative selection criterion to optimize the potential therapeutic. Ribosomal RNA is bound to a solid surface such as, for example, scintillation proximity bead (SPA) by charge interaction. Separate additions to the assay can include tRNA and the associated 64kDa LepA and L27 proteins, as well as other biological targets identified in the methods described above. Biological targets and/or test compounds can be tested alone or in any combination. A representative oxazolidinone or equivalent compound (e. g., eperezolid) is added in a labeled form as described (e. g., 3H-eperezolid) and the ability of test compounds to compete or reduce the binding of the labeled compound is measured. For the tritiated SPA example, measurement can be by liquid scintillation. Alternate probes with alternate methods of measurement (e. g., coupled enzymatic activity, chemical shifts/measurement, fluorescence), however, can also be used. The effective concentrations of compounds that specifically reduce binding to the targets identified as described above are taken as a positive selection for potential therapeutics. Attractive compounds so identified are then tested for selectivity with respect to the toxicity targets identified in the eukaryotic target cells by similar techniques but using eukaryotic target molecules. Proteins can also be bound to selection matrixes by antibodies or by known chemical tags attached to the identified targets (e. g. histidine-metal, streptavidin-biotin, etc.) for these purposes. In particular, iodinated probe with competition of cross-linking by both active and inactive enantiomers of eperezolid can be used to illustrate this particular embodiment. A strain of S. aureus is grown at exponential rate. Aliquots of cells (1 ml/1.5 ml tube) are gently pelleted and resuspended in fresh medium with or without 40 1M active eperezolid (S) or inactive enantiomer (R) and 8 I1M l25I-probe (2 pCi/tube) for 30 minutes. The samples were then treated as described above in Example 12. Examination of the RNA from such procedures shows that the 23S RNA is cross-linked I a particular fashion, e. g. cross-linking is prevented by the active enantiomer (S) but not the inactive enantiomer (R). Separation of RNA on a 1% agarose gel demonstrates that the 23S RNA is specifically cross-linked (data not shown). Separation on 10% TBE urea electrophoresis gels demonstrates that tRNA is also cross-linked (data not shown). An autoradiogram of 10-20% Tris Tricine polyacrylamide analysis of the ribosomal pellets demonstrates cross-linking of a 64 kDa protein (LepA) and an 11 kDa protein (L27) (data not shown). The information taught by cross-linking studies can also be used for structure-based design. Briefly, co-crystals are prepared with an oxazolidinone or equivalent molecule together with one or more of the key components of the interaction as identified and described above. The description of the direct interaction with the relevant binding site is used as a positive guide in the construction of new potential therapeutics. The co-crystal of the same test compounds with the eukaryotic target can be used as a negative selection. By the same rationale, NMR can be used to study the interaction of a suitable test compound (oxazolidinone or equivalent molecule) with any or all of the respective target molecules that have been identified by the cross-linking studies. In this case, either the test compound and/or the biological targets are suitably modified to allow measurements of the site of interaction by standard techniques. As those skilled in the art will appreciate, numerous changes and modifications may be made to the preferred embodiments of the invention without departing from the spirit of the invention. It is intended that all such variations fall within the scope of the invention. The entire disclosure of each publication cited herein is hereby incorporated by reference.

Claims: What is claimed is: 1. A method for identifying a biological target of an oxazolidinone-type antibiotic comprising the steps of: contacting a susceptible cell with an oxazolidinone photoaffinity probe; exposing said photoaffinity probe to light to form a complex between said photoaffinity probe and said biological target; and detecting said complex. 2. The method of claim 1 wherein said photoaffinity probe is detectably labeled. 3. The method of claim 2 wherein said detectable label is enzymatic, chemiluminescent, fluorescent, or radioactive. 4. The method of claim 1 wherein said detecting of said complex is by autoradiography. 5. The method of claim 1 wherein said photoaffinity probe comprises the formula EMI37.1 X and Y are, independently, F, H or CH3 ; R8isH, ForI ; R9 is H, F or OH ; Rl8 is H or F ; Rl9 is H or F ; Rl is H or Cl-C8 alkyl ; L is a bond or-OCH2C (=O) ; and Qis EMI38.1 wherein: Rll is H, CH3, CH2CH3 or cyclopropyl ; and Z is O or S ; or a pharmaceutically acceptable salt thereof. 6. The method of claim 5 wherein X is F, Y is H, Rlo is H, and R11 is CH3. 7. The method of claim 5 wherein said photoaffinity probe is 2- [4- [4- [ (5S)-5- [(Acetylamino) methyl]-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-1-piperazinyl]-2-oxoethyl-4azido-2-hydroxy-5-iodo-l2sI-benzoate. 8. The method of claim 5 wherein said photoaffinity probe is N- [ [ (5S)-3- [4- [4- (4-Azido-2- hydroxy-5-iodo-125I-benzoyl)-1-piperazinyl]-3-fluorophenyl]-2-oxo-5oxazolidinyl] methyl] acetamide. 9. The method of claim 5 wherein said photoaffinity probe is 2- [4- [4- [ (5S)-5- [(Acetylamino)methyl]-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-1-piperazinyl]-2-oxoethyl 4 azido-3-iodo-l25I-benzoate. 10. The method of claim 5 wherein said photoaffinity probe is N- [ [ (5S)-3- [4- [4- (4-Azido-3- iodo-I-benzoyl)-l-piperazinyl]-3-ftuorophenyl]-2-oxo-5-oxazolidinyl] methyl] acetamide. 11. The method of claim 1 wherein said photoaffinity probe. comprises the formula EMI38.2 wherein: X and Y are, independently, F, H or CH3; R12 is N3 or EMI39.1 wherein: R8 is H, F or I ; R9 is H, F or OH ; R18 is H or F and ; Rl9 is H or F ; and Q is EMI39.2 wherein: Rll is H, CH3, CH2CH3 or cyclopropyl ; and ZisOorS ; or a pharmaceutically acceptable salt thereof. 12. The method of claim 11 wherein X is F, Y is H, Rll is CH3, and R12 is EMI39.3 13. The method of claim 11 wherein said photoaffinity probe is N-[[(5S)-3-(4'-Azido-2fluoro [1, 1'-biphenyl]-4-yl)-2-oxo-5-oxazolidinyl] methyl]-T3-acetamide. 14. The method of claim 11 wherein said photoaffinity probe is N- [ [ (5S)-3- (4'-Azido-2- fluoro-3'-iodo [1, 1'-biphenyl]-4-yl)-2-oxo-5-oxazolidinyl] methyl]-T3-acetamide. 15. The method of claim 11 wherein said photoaffinity probe is N-[[(5S)-3-(4'-Azido-2 fluoro-3'-iodo [1, 1'-biphenyl]-4-yl)-2-oxo-5-oxazolidinyl] methyl] ethane-35S-thioamide. 16. The method of claim 11 wherein said photoaffinity probe is N- [ [ (5S)-3- (4'-Azido-2- fluoro-3'-iodo-l'-biphenyl]-4-yl)-2-oxo-5-oxazolidinyl] methyl] acetamide. 17. The method of claim 1 wherein said photoaffinity probe comprises the formula EMI40.1 wherein: X and Y are, independently, F, H or CH3 ; R13 is EMI40.2 wherein: Rl4 is H, N3, halogen, NH2, OH, SH, Cl-C4 alkylamino, Cl-C4 dialkylamino, Cl-C4alkyl, nitrile, carboxamide, Cl-C4 alkoxy, Cl-C4 alkylthio, or Cl-C4 alkoxycarbonyl; and Pis EMI40.3 wherein: Z is O or S ; and R15 is EMI41.1 wherein: R8 is H, F or I ; R9 is H, F or OH ; Rl8 is H or F ; and Rl9 is H or F ; and or a pharmaceutically acceptable salt thereof. 18. The method claim 17 wherein X is F, Y is H, and Rl4 is H. 19. The method of claim 17 wherein said photoaffinity probe is (2E)-3-(4-azido-3-iodo-l25I- phenyl)-N-[[(5S)-3-[3-fluoro-4-(4-pyridinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2propenamide. 20. The method of claim 17 wherein said photoaffinity probe is 4-azido-N- [ [ (5S)-3- [3- fluoro-4-(4-pyridinyl) phenyl]-2-oxo-5-oxazolidinyl] methyl]-2-hydroxy-5-iodo-l25I-benzamide. 21. The method of claim 17 wherein said photoaffinity probe is N- (4-azidophenyl)-N'- [ [ (5S)-3- [3-fluoro-4- (4-pytidinyl) phenyl]-2-oxo-5-oxazolidinyl] methyl] ¯35 S-thiourea. 22. A method of identifying a compound that inhibits binding of a probe to a biological target thereof comprising the steps of: contacting said biological target with a probe, wherein said biological target is ribosomal RNA, tRNA, LepA protein, L27 protein, or any combination thereof; contacting said biological target with a test compound; and comparing the amount of binding between said probe and said biological target in the presence and absence of said test compound, wherein a decrease in the amount of binding between said probe and said biological target in the presence of said test compound indicates that said test compound inhibits binding of said probe to said biological target. 23. The method of claim 22 wherein said biological target is bound to a solid phase. 24. The method of claim 23 wherein said solid phase is a scintillation proximity bead. 25. The method of claim 22 wherein said biological target is 23S ribosomal RNA. 26. The method of claim 25 wherein said biological target is a fragment of 23S ribosomal RNA comprising the peptidyltransferase region. 27. The method of claim 22 wherein said biological target is tRNA. 28. The method of claim 27 wherein said biological target is tRNAfMet. 29. The method of claim 22 wherein said biological target is LepA protein. 30. The method of claim 22 wherein said biological target is L27 ribosomal protein. 31. The method of claim 22 wherein said probe is detectably labeled. 32. The method of claim 31 wherein said detectable label is enzymatic, chemiluminescent, fluorescent, or radioactive. 33. The method of claim 22 wherein said probe is an oxazolidinone compound. 34. The method of claim 33 wherein said oxazolidinone compound is linezolid or eperezolid.

Inventors: COLCA JERRY R, MCDONALD WILLIAM GERALD, SHINABARGER DEAN L, COLCA, JERRY, R., MCDONALD, WILLIAM, GERALD, SHINABARGER, DEAN, L.
Applicants: COLCA JERRY R, MCDONALD WILLIAM GERALD, SHINABARGER DEAN L, UPJOHN CO, COLCA, JERRY, R., MCDONALD, WILLIAM, GERALD, PHARMACIA & UPJOHN COMPANY, SHINABARGER, DEAN, L.
Application year: 2001
Main classification: G01N33
IPC codes: C07D263, C12Q1, G01N33