GLYCOPEPTIDE ANTIBIOTICS CONTAINING A DESMETHYLVANCOSAMINE RESIDUE, COMBINATORIAL LIBRARIES OF SAME AND METHODS OF PRODUCING SAME

Abstract: A glycopeptide of the formula A1-A2-A3-A4-A5-A6-A7, in which each dash represents a covalent bond; wherein the group A1 comprises a modified or unmodified alpha -amino acid residue, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, akylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl; wherein each of the groups A2 to A7 comprises a modified or unmodified alpha -amino acid residue, whereby (i) the group A1 is linked to an amino group on the group A2, (ii) each of the groups A2, A4 and A6 bears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) the group A7 bears a terminal carboxyl, ester, amide, or N-substituted amide group; and wherein one or more of the groups A1 to A7 is linked via a glycosidic bond to one or more glycosidic groups each having one or more sugar residues; wherein at least one of said sugar residues bears one or more substituents of the formula YXR; provided that: A4 is linked to a glycosidic group comprising a glucose residue substituted only by hydroxyl and/or amino groups and by attachement via a glycosidic bond to formula (II).

Description: GLYCOPEPTIDE ANTIBIOTICS CONTAINING A DESMETHYLVANCOSAMINE RESIDUE, COMBINATORIAL LIBRARIES OF SAME AND METHODS OF PRODUCING SAME Field of the Invention The present invention relates to glycopeptide compounds bearing a desmethylvancosamine residue, libraries of such compounds and methods of generating those libraries. Substituent groups are substituted on the carbohydrate moieties of these compounds. The libraries are generated using combinatorial chemical techniques that produce a diverse set of carbohydrate functionalities conjugated to an oligopeptide. Background of the Invention Glycopeptide antibiotics are characterized by having at least one saccharide group chemically bonded to a rigid peptide structure having a cavity or cleft which acts as a binding site for the substrate used in bacterial cell wall synthesis. The glycopeptide antibiotics are further categorized into various subclasses depending on the identity and interconnections of the amino acids comprising the peptide backbone and the number and substitution pattern of the sugar residues in the molecule. The glycopeptide antibiotics are generally active against Gram-positive bacteria but relatively ineffective against Gram-negative bacteria. Most notable among the glycopeptide antibiotics is vancomycin. Vancomycin is produced by Amycolatopsis orientalis, and is often referred to as "the drug of last resort" because it is effective against most multi-drug-resistant gram positive bacteria. However, in recent years vancomycin-resistant strains of some bacteria have emerged. [Cohen M., (1992): Neu H., (1992)]. It is estimated that 5-25% of enterococcal strains in hospitals are now resistant to vancomycin [Axelsen, P.H. et al. (1997)]. Most feared among the bacteria is Staphylococcus aureus, which can result in dangerous respiratory and blood infections. Vancomycin- resistant and vancomycin-insensitive strains of this bacterium have also been recently reported [Milewski (1996)]. The structural formula of vancomycin is shown below and is characterized by a disaccharide moiety covalently linked to a heptapeptide structure. The structure of vancomycin places it in a class of molecules referred to as the "dalbaheptides." [Malabarba A., et al. (1997a)] Dalbaheptides in general are characterized by the presence of seven amino acids linked together by peptide bonds and held in a rigid conformation by cross-links through the aromatic substituent groups of at least five of the amino acid residues. In the heptapeptide structure of vancomycin, which is commonly referred to as the "aglycone" of vancomycin, the aromatic side-chains of amino acids 2, 4, and 6 are fused together through ether linkages. The side-chains of amino acids 5 and 7 are joined via a carbon-carbon bond. Amino acids 1 and 3 are leucine and asparagine, respectively. Other naturally occurring glycopeptide antibiotics are similar to vancomycin in that they have a glucose residue linked to the aromatic substituent on amino acid 4 through formation of a bond with a phenolic hydroxyl group. The glucose residue, in turn, is linked through its vicinal hydroxyl position to a unique amino sugar, L-vancosamine. The sugars have been separately removed from glycopeptide antibiotics, and it has been found that the presence of both sugars enhances the pharmacokinetic properties of this class of antibiotics. [Nagarajan R. (1988), (1991), (1993] (I) The anti-microbial activity of vancomycin is known to be due to its ability to interfere with biosynthesis of the bacterial cell wall. [Nagarajan R. (1993)]. NMR evidence shows that the heptapeptide chain of vancomycin forms a number of hydrogen bonds with the D-alanyl-D- alanine terminus of the disaccharide-pentapeptide precursors used to form the cell wall. [see. e.g., Prowse W., et al. (1995); Pierce C, et al. (1995); Williams D. et al. (1988)]. This interaction of vancomycin with cell wall precursors apparently inhibits or prevents the subsequent transglycosylation and/or transpeptidation steps of cell wall assembly. Supporting this mode of action is the fact that vancomycin-resistant strains of bacteria are found to produce a pentapeptide precursor terminating in a D-alanyl-D-lactate sequence. It is hypothesized that the reduced effectiveness of vancomycin against resistant strains is due to reduced hydrogen bonding interactions between the drug and the D-alanyl-D-lactate substrate. The affinity of vancomycin for D-alanyl-D-lactate is estimated to be 2-3 orders of magnitude (4J kcal/mol) less than for D-alanyl-D-alanine. [Walsh C. (1993)]. The sugar residues of vancomycin and other glycopeptide antibiotics have been shown to affect binding activities. Structural changes in the sugar residues can produce significant changes in antibiotic activity. [Malabarba (1997), Nagarajan, R. (1993)] It has been proposed that the sugar residues on the glycopeptide antibiotics may enhance the avidity of these molecules for surface-bound peptide ligands. At least two different mechanisms for enhancing avidity have been proposed. [Kannan (1988), Gerhard (1993), Allen (1997)] For example, it has been proposed that the biological activity of vancomycin, along with that of many other glycopeptide antibiotics, is enhanced by dimerization due to bonding interactions at the convex (non-ligand binding) face of the molecule. [Williams D., et al. (1993); Gerhard U., et al., (1993)] Dimerization is believed to be facilitated by the disaccharide groups of the vancomycin molecule, and is thought to influence activity by increasing the avidity of vancomycin for surface-bound D-Ala-D-Ala peptide ligands. [Williams, ( 1998)] Structural evidence for dimerization has been obtained from both NMR and crystallographic studies, and it has been found that there are significant differences in the stability of the dimers formed in solution by different glycopeptide antibiotics. [MacKay (1994)] It is proposed that differences in the dimerization constants may account at least partially for the remarkable differences in biological activity of different glycopeptide antibiotics which otherwise have very similar binding affinities for the natural d-Ala-d-Ala substrate. [Williams (1998)] A second mechanism for enhancing activity has also been proposed for the glycopeptide antibiotic teicoplanin, which contains an N-alkyl chain on one of the sugars. It is suggested that this N-alkyl chain increases the effective avidity of teicoplanin for surface-bound D-Ala- D-Ala ligands by interacting with the membrane, thus "anchoring" the teicoplanin molecule at the membrane surface. [Beauregard (1995)] It should be noted that the attachment of hydrophobic substituents to the vancomycin carbohydrate moiety appears to enhance activity against vancomycin-resistant strains. For example, attaching a hydrophobic group to the vancosamine sugar by alkylation on the amine nitrogen increases, activity against vancomycin-resistant strains by two orders of magnitude. [Nagarajan (1991)] It is speculated that the lipophilic groups locate the antibiotic at the cell surface and make ligand binding an intramolecular process, which may partially overcome the decreased binding affinity for D-Ala-D-Lac. Hence, although the sugars on the glycopeptide antibiotics do not appear to interact substantially with the peptide substrates, they play a very important role in increasing the biological activity. Therefore, one potentially successful strategy for the design of new antibacterial agents based on the glycopeptide class of antibiotics involves modifying the carbohydrate portions of the molecules. [Malabarba (1997a)] Related members of the vancomycin class of glycopeptide antibiotics include the ristocetins, the eremomycins, the avoparcins and teicoplanin. Several of these compounds are shown, together with vancomycin in Figure 1. The chemical structures of all of these compounds include a dalbaheptide structure as the aglycone core, with minor differences in the amino acids and in cross-linking, but differ from each other most distinctively in terms of the nature of the sugar residues as well as the number and points of attachment of sugar residues to the aglycone core. International (PCT) application number PCT US99/15845, filed July 14, 1999 (publication date on or about January 20, 2000) entitled "Glycopeptide Antibiotics, Combinatorial Libraries of Glycopeptide Antibiotics and Methods of Producing Same," and which is incorporated herein by reference, discloses glycopeptide compounds in which the substituted sugar residues are attached to the peptide core through glycosidic linkages. Co-pending application serial number 60/115,595, filed January 12, 1999 and entitled "Substituted Alpha-Linked Disaccharides," which is incorporated herein by reference, discloses disaccharide compounds comprising two hexose residues joined by an alpha glycosidic linkage. These compounds display activity as transglycosylase inhibitors. Derivatives of vancomycin in which the amino group of a vancosamine or epi-vancosamine residue bears a variety of substituent groups, including alkyl, alkanoyl, and aralkvl are disclosed in U.S. Patent Nos. 4,639,433; 4,643,987; 4,698,327; and 5,591 ,714: and in Zelenitsky, S. et al. (1997). However, these references do not disclose compounds bearing an N-substituted desmethylvancosamine residue. Typically, changes in the substitution pattern or stereochemistry of vancomycin lead to decreased activity. For example, substitution of epi-vancosamine, in which the hydroxyl group is in the equatorial position, for the vancosamine sugar leads to a substantial reduction in antimicrobial activity relative to vancomycin. [Malabarba (1997a)] Accordingly, removal of the methyl substituent geminal to the amino group in the vancosamine residue would not have been expected to increase activity. SUMMARY OF THE INVENTION This invention is directed to glycopeptide of the formula Aι-A -A - -A 5 -A -A 7 . in which each dash represents a covalent bond; wherein the group Ai comprises a modified or unmodified α-amino acid residue, alkyl, aryl, aralkyl, alkanoyl, aroyl. aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl; wherein each of the groups A to A 7 comprises a modified or unmodified α-amino acid residue, whereby (i) the group Ai is linked to an amino group on the group A 2 , (ii) each of the groups A , A and A^ bears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) the group A 7 bears a terminal carboxyl, ester, amide, or N- substituted amide group; and wherein one or more of the groups A] to A 7 is linked via a glycosidic bond to one or more glycosidic groups each having one or more sugar residues; wherein at least one of said sugar residues bears one or more substituents of the formula YXR in which the group Y is a single bond, O, NR, or S; the group X is O, NR,, S, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NRι)O, C(O)NRι, or halo (in which case Y and R are absent); and R is hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic- alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; Ri is hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl. aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; and any pharmaceutically acceptable salts thereof; provided that: X and Y are not both O; X and Y are not S and O, or O and S, respectively; and if two or more of said substituents are present, they can be the same or different; and provided that: A is linked to a glycosidic group comprising a glucose residue substituted only by hydroxyl and/or amino groups and by attachment via a glycosidic bond to wherein Z, is a single bond, NR- t , SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR- O, or C(O)NR- 4 ; Z 2 is a single bond, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR 5 )O, or C(O)NR 5 ; R 2 , R 3 , R 4 and R 5 are independently hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; and wherein R is as defined above; provided that when Z? is SO , C(O)O, C(O)S, C(S)O, C(S)S or C(NR 5 )O, then R 2 is not hydrogen. This invention is further directed to a library of glycopeptide compounds. Consistent with the objectives of the present invention a process is disclosed for glycosylating a glycopeptide antibiotic, pseudoaglycone, or glycone comprising the steps of attaching at least one sugar bearing one or more desired substituent groups or at least one protected unsubstituted sugar to a nucleophilic group of a glycopeptide antibiotic, pseudoaglycone, or glycone under conditions that permit a glycosylation reaction to take place. Typically, the glycosylation reaction involves nucleophilic attack of an activated group on the sugar by a nucleophile found in the glycopeptide antibiotic, pseudoaglycone, or glycone. In a particular embodiment of the invention, the activated group includes an activated anomeric sulfoxide. In a preferred embodiment, the glycopeptide antibiotic is vancomycin, the pseudoaglycone is the pseudoaglycone of vancomycin and the aglycone is the aglycone of vancomycin. In general, the process is directed to the preparation of a carbohydrate-modified glycopeptide derivative comprising contacting a sugar having an anomeric sulfoxide substituent with a pseudoglycone or aglycone under conditions that permit a sulfoxide glycosylation reaction to take place. This reaction provides a glycopeptide having a modified carbohydrate group. The sulfoxide glycosylation reaction is generally believed to involve a nucleophilic group of the pseuodoglycone or aglycone, which attacks an activated anomeric sulfoxide moiety of the sugar to form a glycosidic linkage. A variety of conditions can be utilized to effect the sulfoxide glycosylation reaction, which can be permitted to take place in solution or over a solid phase. In preferred embodiments, the conditions include effective amounts of trifluoromethanesulfonic anhydride and 2,6-di-t-butylmethylpyridine. Most preferably, the conditions include the presence of boron trifluoride. The present invention contemplates that the sugar comprises a monosaccharide bearing an anomeric sulfoxide substituent, for example. The monosaccharide can then be allowed to come into contact with a pseudoaglycone or an agylcone, as the case may be. The sugar may also comprise a disaccharide bearing an anomeric sulfoxide substituent. The disaccharide is contacted with an aglycone, for instance. In certain applications, there may be advantages to be gained by utilizing a sugar having an anomeric sulfoxide substituent, which sugar also bears an unhindered ester at the C-2 position. Examples of unhindered esters include acetate esters, propionate esters and the like. Use of such C-2 substituted sugars is expected to give rise to the formation of a β glycosidic linkages. In the process of the invention, when a monosaccharide is contacted with an aglycone, the resulting glycosylated product might be subjected to a second glycosylation reaction (e.g., a second sulfoxide glycosylation reaction) involving a second sugar. Moreover, the second sugar can be an azido sugar. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 contains structure diagrams of vancomycin and related glycopeptide antibiotics. Figures 2A and 2B are graphs showing inhibition of peptidoglycan synthesis by compounds of this invention and controls. DETAILED DESCRIPTION OF THE INVENTION Definitions A "glycoconjugate" comprises any molecule linked to at least one carbohydrate of any size. The molecule can be a peptide or protein, a nucleic acid, a small molecule, a lipid, or another carbohydrate; it may be of natural or non-natural origin. A "glycopeptide" is a glycoconjugate comprising a peptide linked to at least one carbohydrate. A "glycopeptide antibiotic" is one of the naturally occurring glycopeptides with antibacterial activity, including, e.g., vancomycin, teicoplanin, ristocetin, chloroeremomycin and avoparicin. An "aglycone" is the result of removing the carbohydrate residues from a glycopeptide, leaving only a peptide core. A "pseudoaglycone" is the result of removing only one of two sugar residues of a disaccharide residue linked to residue of a glycopeptide. Thus, a pseudoaglycone comprises an aglycone in which A 4 is linked to a monosaccharide residue. A "dalbaheptide" is a glycopeptide containing a heptapeptide moiety which is held in a rigid conformation by cross-links between the aromatic substituent groups of at least five of the seven α-amino acid residues, including a cross-link comprising a direct carbon-carbon bond between the aryl substituents of amino acid residues 5 and 7, and aryl ether cross-links between the substituents of amino acid residues 2 and 4, and 4 and 6. Amino acid residues 2 and 4-7 in different dalbaheptides are those found in the naturally occurring glycopeptide antibiotics. These amino acid residues differ only in that residues 2 and 6 do not always have a chlorine substituent on their aromatic rings, and in that substitution on free hydroxyl or amino groups may be present. Amino acid residues 1 and 3 may differ substantially in different dalbaheptides; if both bear aryl substituents, these may be cross-linked. Molecules having a dalbaheptide structure include, e.g., the glycopeptide antibiotics mentioned above. The term "alkyl" refers to a linear or branched acyclic or non-aromatic cyclic group having from one to twenty carbon atoms connected by single or multiple bonds. An alkyl group may be substituted by one or more of halo, hydroxyl, protected hydroxyl, amino, nitro. cyano, alkoxy, aryloxy, aralkyloxy, COOH, aroyloxy, alkylamino, dialkylamino, trialkylarnrnoniurn, alkylthio, arylthio, alkanoyl, alkanoyloxy, alkanoylamido, alkylsulfonyl, arylsulfonyl, aroyl, aralkanoyl, heterocyclic, CONH 2 , CONH-alkyl, CON(alkyl) 2 , COO-aralkyl, COO-aryl or COO-alkyl. The term "aryl" refers to a group derived from a non-heterocyclic aromatic compound having from six to twenty carbon atoms and from one to four rings which may be fused or connected by single bonds. An aryl group may be substituted by one or more of alkyl. aralkyl, heterocyclic, heterocyclic-alkyl, heterocyclic-carbonyl, halo, hydroxyl, protected hydroxyl. amino, hydrazino, alkylhydrazino, arylhydrazino, nitro, cyano, alkoxy, aryloxy, aralkyloxy, aroyloxy, alkylamino, dialkylamino, trialkylarnrnoniurn, alkylthio, arylthio, alkanoyl, alkanoyloxy, alkanoylamido, alkylsulfonyl, arylsulfonyl, aroyl, aralkanoyl, COO-alkyl, COO-aralkyl, COO-aryl. CONH 2 , CONH-alkyl or CON(alkyl) 2 . The term "aralkyl" refers to an alkyl group substituted by an aryl group. The term "heterocyclic" refers to a group derived from a heterocyclic compound having from one to four rings, which may be fused or connected by single bonds; said compound having from three to twenty ring atoms which may be carbon, nitrogen, oxygen, sulfur or phosphorus. A heterocyclic group may be substituted by one or more of alkyl, aryl, aralkyl, halo, hydroxyl, protected hydroxyl, amino, hydrazino, alkylhydrazino, arylhydrazino, nitro, cyano, alkoxy, aryloxy, aralkyloxy, aroyloxy, alkylamino, dialkylamino, trialkylammonium, alkylthio, arylthio, alkanoyl, alkanoyloxy, alkanoylamido, alkylsulfonyl, arylsulfonyl, aroyl, aralkanoyl, COO-alkyl, COO-aralkyl, COO-aryl, CONH 2 , CONH-alkyl or CON(alkyl) 2 . The terms "alkoxy," "aryloxy" and "aralkyloxy" refer to groups derived from bonding an oxygen atom to an alkyl, aryl or aralkyl group, respectively. The terms "alkanoyl," "aroyl" and "aralkanoyl" refer to groups derived from bonding a carbonyl to an alkyl, aryl or aralkyl group, respectively. The terms "heterocyclic-alkyl" and "heterocyclic-carbonyl" refer to groups derived from bonding a heterocyclic group to an alkyl or a carbonyl group, respectively. The term "heterocyclic-alkyl-carbonyl" refers to a group derived from bonding a heterocyclic-alkyl group to a carbonyl group. The term "protected hydroxyl" refers to a hydroxyl group bonded to a group which is easily removed to regenerate the free hydroxyl group by treatment with acid or base, by reduction, or by exposure to light. The term "Lewis acid", as used herein, refers to any substance that can accept an electron pair from a base, with the exception of the mineral acids and organic carboxylic acids. The term "organic solvent", as used herein, refers to non-aqueous solvents, preferably to ketones, halogenated solvents, ethers, esters and non-heterocyclic aromatic solvents. A "chemical library" is a synthesized set of compounds having different structures. The chemical library may be screened for biological activity to identify individual active compounds of interest. A "glycosyl donor" is a sugar or glycosidic residue that bears an anomeric leaving group, preferably a sulfoxide, which may be activated to render the anomeric carbon susceptible to reaction with a nucleophile to displace the activated group, thereby forming a glycosidic bond. The term "leaving group" as used herein is a group easily displaced from a sulfonyl group by a nucleophile. Examples of leaving groups are halo, alkoxy, aryloxy, alkanoyloxy and arylsulfonyloxy. The term "DMF" refers to N-N-dimethylformamide; "THF" refers to tetrahydrofuran; "TFA" refers to trifluoroacetic acid; "EtOAc" refers to ethyl acetate; "MeOH" refers to methanol; "MeCN" refers to acetonitrile; "Tf ' refers to the trifluoroacetyl group; "DMSO" refers to dimethyl sulfoxide; "DIEA" refers to diisopropylethylamine; "All" in structural formulas refers to the allyl group; "Fmoc" refers to 9-fluorenylmethyloxycarbonyl; "HOBt" refers to 1- hydroxybenzotriazole and "OBt" to the 1 -oxybenzotriazolyl group; "PyBOP" refers to benzotriazol-1-yl-oxytripyrrolidine-phosphonium hexafluorophosphate; "Su" refers to the succinimidyl group; "HBTU" refers to O-benzotriazol-l-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate; "aloe" refers to allyloxycarbonyl; and "CBz" refers to benzy loxycarbonyloxy . The glycopeptide compositions of this invention have the formula Aι-A 2 -A 3 -A -A 5 -A 6 -A 7 , in which each dash represents a covalent bond; wherein the group Ai comprises a modified or unmodified α-amino acid residue, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl; wherein each of the groups A 2 to A 7 comprises a modified or unmodified α-amino acid residue, whereby (i) the group Ai is linked to an amino group on the group A 2 , (ii) each of the groups A 2 , A and A bears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) the group A 7 bears a terminal carboxyl, ester, amide, or N- substituted amide group. It is further required that one or more of the groups A, to A 7 is linked via a glycosidic bond to one or more glycosidic groups each having one or more sugar residues; wherein at least one of said sugar residues bears one or more substituents of the formula YXR in which the group Y is a single bond, O, NR, or S; the group X is O, NR,, S, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR,)O, C(O)NRι, or halo (in which case Y and R are absent); and R and R, are independently hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; and any pharmaceutically acceptable salts thereof; provided that: X and Y are not both O; X and Y are not S and O, or O and S, respectively; and if two or more of said substituents are present, they can be the same or different; and provided that: A 4 is linked to a glycosidic group comprising a glucose residue substituted only by hydroxyl and/or amino groups and by attachment via a glycosidic bond to wherein Z, is a single bond, NIL,, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR- O, or C(O)NR-,; Z 2 is a single bond, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR 5 )O, or C(O)NR 5 ; R 2 , R3, R4 and R 5 are independently hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; and wherein R is as defined above; provided that when Z 2 is SO 2 , C(O)O, C(O)S, C(S)O, C(S)S or C(NR 5 )O, then R 2 is not hydrogen. In an embodiment of the invention, the substitution on the glucose residue, other than the desmethylvancosamine residue, is not limited to hydroxyl and/or amino groups as described above. In another embodiment of the invention, the glycopeptide has the formula A 1 -A 2 -A 3 -A -A 5 - A 6 -A 7 , in which each dash represents a covalent bond; wherein the group Ai comprises a modified or unmodified α-amino acid residue, alkyl, aryl, aralkyl, alkanoyl. aroyl. aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl- carbonyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl wherein each of the groups A 2 to A 7 comprises a modified or unmodified α-amino acid residue, whereby (i) the group A, is linked to an amino group on the group A 2 , (ii) each of the groups A 2 , A 4 and A 6 bears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) the group A 7 bears a terminal carboxyl, ester, amide, or N- substituted amide group; and wherein one or more of the groups A, to A 7 is linked via a glycosidic bond to one or more glycosidic groups each having one or more substituted or unsubstituted sugar residues, provided that A is linked to a glycosidic group comprising a glucose residue substituted only by hydroxyl and/or amino groups and by attachment via a glycosidic bond to wherein Z, is a single bond, NR 4 , SO 2 , C(O)O, C(O)S, C(S)0. C(S)S, C(NR4)O, or C(O)NR 4 ; Z 2 is a single bond, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR 5 )O, or C(O)NR 5 ; R, R 2 , R 3 , R 4 and R 5 are independently hydrogen, alkyl, aryl, aralkyl. alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; and any pharmaceutically acceptable salts thereof; provided that when Z 2 is SO 2 , C(O)O, C(O)S, C(S)O, C(S)S or C(NR 5 )O, then R 2 is not hydrogen. Modified amino acid residues include amino acid residues whose aromatic groups have been substituted by halo, alkyl, alkoxy, alkanoyl, or other groups easily introduced by electrophilic substitution reactions or by reaction of phenolic hydroxyl groups with alkylating or acylating agents; and amino acid residues which have protecting groups or other easily introduced substituents on their hydroxyl or amino groups, including, but not limited to alkyl, alkanoyl, aroyl, aralkyl, aralkanoyl, carbamoyl, alkyloxycarbonyl, aralkyloxycarbonyl, aryloxycarbonyl, alkylsulfonyl, arylsulfonyl, heterocyclic, heterocyclic-alkyl or heterocyclic- carbonyl substituents. Examples of preferred protecting groups include acetyl, allyloxycarbonyl (aloe), CBz, allyl, benzyl, p-methoxybenzyl and methyl. Modifications of hydroxyl groups occur on phenolic hydroxyl groups, benzylic hydroxyl groups, or aliphatic hydroxyl groups. Other amino acid residues, in addition to A 2 , A 4 and A 6 , may be cross- linked through their aromatic substituent groups. Preferably, residues A 2 to A 7 of the glycopeptide are linked sequentially by peptide bonds and are cross-linked as in a dalbaheptide, as defined hereinabove. The preferred glycopeptides thus have a peptide core in which the residues are linked as in the natural glycopeptide antibiotics, as shown in Figure 1. Substitution of different amino acids at A is permitted, as are modified amino acid residues at all positions, as described hereinabove. In a preferred embodiment of this invention, residue A, is an α-amino acid, which may be substituted on the terminal amino group by alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic alkyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl, and the structures and interconnections of A, to A 7 are those of vancomycin, i.e., the glycopeptide has the heptapeptide core of vancomycin, subject to the amino acid modifications and substitutions on A, and A described hereinabove. The glycopeptides of this invention contain at least one glycosidic group attached through a glycosidic bond to the residues A, to A 7 . In all of the glycopeptides of this invention, a glycosidic group is linked to residue A-j; this glycosidic group comprises a glucose residue that is attached directly to A . The glucose residue is in turn linked through a glycosidic bond to a desmethylvancosamine residue. Preferably, the glucose residue is substituted only by hydroxyl groups, amino groups, or a combination thereof, in addition to the desmethylvancosamine residue, and more preferably, the glucose residue is not substituted by any amino groups. As depicted above, the desmethylvancosamine residue lacks the methyl group which is geminal to the amino group in the naturally occurring vancosamines. Preferably, the glycosidic group attached to A4 is a disaccharide consisting only of a glucose residue and a desmethylvancosamine residue. It is further preferred that no other position on the glycopeptide is substituted by a glycosidic group. In a preferred embodiment of the invention, Z 2 is a single bond and R 2 is hydrogen, alkyl, alkanoyl, aroyl or aralkanoyl. It is further preferred that R 3 is hydrogen and Z, is a single bond, and still more preferred that R is alkyl, aralkyl, alkanoyl, aroyl or aralkanoyl. For example, in compound (9), R is aralkyl (4-(4-chlorophenyl)benzyl), R 3 is hydrogen and Z, is a single bond. In a preferred embodiment of this invention, the compounds are prepared by glycosylation of a pseudoaglycone with a glycosylating agent derived from a desmethylvancosamine. Preferably, the glycosylating agent is a desmethylvancosamine bearing an anomeric sulfoxide group. An example of such a glycosylation reaction between a partially protected vancomycin pseudoaglycone and a protected desmethylvancosamine bearing an anomeric phenyl sulfoxide substituent is shown in Scheme 2. The compounds of this invention are also accessible via glycosylation of an aglycone with a glycosylating agent comprising a glucose residue and a desmethylvancosamine residue. The chemical library of compounds of this invention is prepared to explore the effects of introducing a large number of different substituents on glycopeptides on biological activity, especially substitutions on the sugar residues. In any preparation of a chemical library, at least two steps are performed, each of which introduces a substituent group on the glycopeptide. A combinatorial format is established in which many different predetermined substituent groups are introduced independently at each of at least two positions, resulting in a library containing a large number of glycopeptides, wherein each possible combination of the predetermined substituent groups is represented. For example, if three positions are to be substituted and 36 different substituent groups (3 sets of 12) are chosen, 1 of each set of 12 to be substituted at each position, the total number of unique compounds (each of which bears 3 substituent groups) in the library will be 12x12x12=1,728. It is readily apparent that, when a combinatorial synthesis is performed in an automated system, a large number of related compounds may be prepared relatively quickly. Methods for performing combinatorial synthesis are well known and are described in several review articles. [Thompson (1996), Gallop (1994), Gordon (1994), Terrett (1995)] Substituents are introduced on the glycopeptide library compounds of this invention in two ways: (1) by using glycosylation reactions to attach sugars bearing desired substituent groups to hydroxyl groups on various positions of glycopeptide antibiotics, aglycones, or pseudoaglycones, as described in detail hereinbelow; and (2) by using glycosylation reactions to attach protected unsubstituted sugars, followed by partial deprotection of the sugar and introduction of a substituent on a deprotected amino, hydroxyl or thiol group via known reactions, e.g., alkylation, reductive amination, esterification. In construction of the library of this invention, at least two steps are carried out in a combinatorial format. These steps are selected independently from the two reaction schemes outlined hereinabove, such that a library is constructed using either scheme exclusively or a combination of the two. A modified sulfoxide glycosylation of the aglycone phenolic hydroxyl group may be accomplished using an acetate or other unhindered ester at C-2 of the sugar as a neighboring group. In this modified glycosylation, as in the preferred glycosylation procedure utilizing activated monosaccharide anomeric sulfoxides, the leaving group at the anomeric center is a sulfoxide moiety which is activated by trifiuoromethanesulfonic anhydride (Tf 2 O) in the presence of 2,6-di-t-butylmethylpyridine. The modification to the glycosylation procedure involves addition of BF 3 to the reaction. Without being bound to theory, it is believed that the presence of BF 3 prevents formation of the undesired ortho-ester side product which is unstable in the presence of acid. Use of the modified procedure leads to the desired β glycosidic linkage. The use of BF 3 is an improvement because previously the presence of a very bulky ester at C-2 (e.g., pivalate) was required to prevent formation of the undesired ortho-ester during formation of a β glycosidic linkage by the sulfoxide method using neighboring group participation. These bulky esters can be very difficult to remove, except under strongly basic conditions. It is preferred to perform the aforementioned glycosylation reactions on a polymeric resin, preferably after coupling the carboxylic acid functionality of these compounds to a suitable resin. In order to attach the carboxylic acid group to the resin, it must first be selectively deprotected. Use of a p-nitrobenzyl ester as a protecting group for the carboxylic acid is preferred to facilitate selective deprotection of the carboxylic acid in the presence of protected hydroxyl groups. A suitable resin is a cross-linked polymer insoluble in the reaction solvent which is suitably functionalized for attachment, e.g., SASRIN (Wang's resin). Once coupled to the resin, the differentially protected hydroxyl group on the attached sugar is deprotected. Alternatively, this hydroxyl group is freed before attachment to the resin, since the hydroxyl group does not interfere with the coupling reaction. The free hydroxyl group then serves as the nucleophile in a second glycosylation reaction. In this second glycosylation. the hydroxyl is glycosylated, preferably in a solid phase reaction, with a variety of azido sugars. Following the glycosylation reaction, the azido groups are reduced and the resulting amino groups are then derivatized. The solid phase portion of the library construction can be carried out using a parallel synthesis or a mix and split strategy. The carbohydrate-modified glycopeptide derivatives would then be deprotected and cleaved from the resin. This set of compounds would then be assayed for peptide binding and antibacterial activity. When it is desired to remove protecting groups from any of the compounds of this invention, their removal is accomplished using methods well known to those skilled in the art. The preferred method for removal of protecting groups is as follows. Aloe groups on amines, and allyl esters or allyl ethers are removed by using Pd(0) mediated reactions, e.g., [Ph 3 P] 2 Pd(II)Cl 2 and Bu 3 SnH in 1 :1 acetic acid:DMF. Acetate protecting groups are removed using hydrazine in THF/methanol. The following examples are presented in order to illustrate various aspects of the present invention, but are not intended to limit it. EXAMPLES EXAMPLE 1 : Phenyl 3-(N-allyloxycarbonyl)amino-4-O-acetyl-l-sulfinyl-2,3,6-trideoxy- α,β-L-lyxo-hexopyranoside (4). Preparation of the title compound is illustrated in Scheme 1 : Scheme 1 Scheme 1 (a) i. PPh 3 , 10:1 THF:H 2 O, 60°C, 2h; ii. Alloc-Su, THF, it, 3h, 96% over 2 steps; (b) Ac 2 O, Et 3 N, DMAP, CH 2 C1 2 , r.t., lh, 97%; (c) mCPBA, CH 2 C1 2 , -78°C to -20°C, lh, 96%; a) Phenyl 3-(N-allyloxycarbonyl)amino-l-thio-2J,6-trideoxy~α,β-L-lyxo- hexopyranoside (2). To a solution of 1 (66 mg, 0.25 mmol) in 4 mL 10: 1 THF:H 2 O is added PPh 3 (130 mg, 0.50 mmol). The reaction is stirred at 60°C for 2 hours and cooled to room temperature. To the reaction mixture is added a solution of Alloc-Su (74 mg, 0.37 mmol) in 2 mL of THF. The reaction is stirred at room temperature for 3 hours, evaporated to dryness and purified by flash chromatography (15% EtOAc/CH 2 Cl2) to give 77 mg (96%) of 2 as a colorless oil. (α:β=2:l). α anomer: R f =0.25 (15% EtOAc/CH 2 Cl 2 ) Η NMR (CDC1 3 , 500 MHz) δ 7.48- 7.44 (m, 2H, Ph-H), 7.33-7.23 (m, 3H, Ph-H), 5.98-5.88 (m, 1H), 5.63 (d, J=5.5Hz, 1H, H-l), 5.32 (br d, J=17.1 Hz, 1H), 5.23 (br d, J=9.5 Hz, 1H), 5.22 (br, 1H, NH), 4.59 (br d, J=5.0Hz, 2H), 4.53 (q, J=6.5Hz, 1H, H-5), 4.10 (m, 1H, H-3), 3.68 (br s, 1H, H-4), 2.18-2.07 (m, 2H, H-2a, H-2e), 1.23 (d, J=7.0Hz, 3H, H-6 Me); β anomer: R f =0.30 (15% EtOAc/CH 2 Cl 2 ) Η NMR (CDC1 3 , 500 MHz) δ 7.50 (m, 2H, Ph-H), 7.34-7.28 (m, 3H, Ph-H), 5.97-5.87 (m, IH), 5.31 (dd, J=1.4Hz, 17.1Hz, IH), 5.30 (br, 1H. NH), 5.22 (dd, J=1.4Hz, 11.0Hz, IH), 4.80 (dd, J=1.9Hz, 12.0Hz, IH, H-l), 4.56 (br d, J=5.7 Hz, 2H), 3.84 (m, IH, H-3), 3.67 (q, J=6.6Hz, IH, H-5), 3.54 (d, J=2.0 Hz, IH, H-4), 2J9 (ddd, J=1.9Hz, 3.2Hz, 12.4Hz, IH, H-2e), 1.66 (q, J=12.4Hz, IH, H-2a), 1.32 (d, J=6.6Hz, H-6 Me). b) Phenyl 3-(N-allyloxycarbonyl)amino-4-O-acetyl-l-thio-2J,6-trideoxy~α,β-L-lyxo- hexopyranoside (3). To a solution of 3 (77 mg, 2.4 mmol) in CH 2 CI 2 is added triethylamine (0J33 mL, 0.95 mmol) followed by acetic anhydride (0.045 ml, 0.48 mmol) and DMAP (5.8 mg, 0.048 mmol). The reaction is stirred at room temperature for 1 hour and is quenched with methanol. The reaction mixture is evaporated to a white solid and the solid is purified by flash chromatography (10% EtOAc/CH 2 Cl 2 ) to give 84 mg (97%) of 3 . as a white solid. (α:β=2:l as an inseparable mixture) R f =0.35 (10% EtOAc/CH 2 Cl 2 ). Η NMR (CDC1 3 , 500 MHz) δ 7.53-7.45 (m, Ph-H), 7.34-7.23 (m, Ph-H), 5.98-5.87 (m), 5.70 (d, J=5.5Hz, α-H-1), 5.34-5.22 (m), 5.20 (br d, J=2.1Hz, H-4), 5.09 (br d, J=3.0Hz, H-4), 4.85 (dd, J=1.8Hz, 11.7Hz, β-H-1), 4.76-4.69 (m), 4.59-4.53 (m), 4.29 (m, H-3), 4.03 (m, H-3), 3.73 (q, J=6.5Hz, H-5), 2.26-2.19 (m, αH-2a, H-2e), 2.18 (s, -OAc), 2.10 (br dd, J=4.8Hz, 13.7Hz, β - H-2e), 1.82 (q, J=12.5Hz, β-H-2a), 1.21 (d, J=6.5Hz, H-6 Me), 1 J2 (d, J=6.6Hz, H-6 Me). c) Phenyl 3-(N-allyloxycarbonyl)amino-4-O-acetyl-l-sulfinyl-2,3,6-trideoxy— ,β-L- lyxo-hexopyranoside (4). To a solution of 3 (29 mg, 0.079 mmol) in 3 ml of CH 2 C1 2 at -70°C is added mCPBA (23 mg of 60%) purity, 0.079 mmol). The reaction is slowly warmed up to -20°C in 45 minutes and kept at -25°C to -20°C for 15 minutes before being quenched with 0J mL of dimethyl sulfide. The reaction is extracted with 5 mL saturated aqueous NaHCO 3 solution. The aqueous layer is further extracted with CH 2 CI 2 (5 mLx3). The CH2CI2 layers are combined and dried over anhydrous sodium sulfate, filtered, concentrated to a colorless oil. The oil was purified by flash chromatography (60% EtOAc/PE) to give 29 mg (96%) of 4 as a white solid. R f =0.33, 0.30, 0.25 (60% EtOAc/PE). EXAMPLE 2: Preparation of Desmethylvancosamine N-(4-(4-chlorophenyl)benzyl) desmethylvancomycin (9). Preparation of compound (9) is illustrated in Scheme 2: Scheme 2. (a) 2 eq BF 3 Et 2 0, 2 eq Tf 2 0, CH 2 CI 2 Jhen 2 eq 4,Et 2 0, -78°C to -10°C, 1 h, 71 % plus 25% recovered 5; (b) 3% hydrazine, allyl alcohol MeOH=1 2, rt, 24 h, 53%, (c) 50 eq Bu 3 SnH, 1 eq PdCI 2 (PPh 3 ) 2 , DMF/AcOH=1 1 , rt, 10 mins, 79%, 4,4'-chlorobιphenylaldehyde, D!EA,NaBH 3 CN, 65°C, 3h, 62% a) Glycosylation of pseudoaglycone (5) to give (6). The pseudoaglycone 5 (214 mg, 0J22 mmol) is azeotroped with toluene three times (1 mL each), dissolved in 6 mL CH 2 C1 2 and then cooled to -78°C. BF 3 OEt 2 (30 μL, 0.244 mmol) is added followed by triflic anhydride (20.5 μL, 0J22 mmol). A solution of sulfoxide 4 (93 mg, 0.244 mmol) in 0.3 mL Et 2 θ is added dropwise over 15 minutes. The reaction is allowed to warm up to -10°C in 1 hour and then quenched with a mixture of 200 μL methanol and 200 μL DIEA. The solvents are removed under reduced pressure and the residue is purified by flash chromatography (2.5 - 4% MeOH/CH 2 Cl 2 ) to give 54 mg (25%) of recovered starting material 5 and 174 mg (71%) of 6 as a white solid. R f = 0.28 (5% MeOH/CH 2 Cl 2 ), FAB-MS [M+Na] + Calc. 2036.6319, found 2036.6352. b) Deprotection of acetates (6) to give (7). Compound 6 (12 mg, 0.0060 mmol) is dissolved in 700 μL of 3% NH 2 ' NH 2 solution in allyl alcohol/methanol=l :2. The reaction is stirred at room temperature for 24 hours and then quenched by addition of 100 μL acetic acid. All the solvents are removed under reduced pressure and the residue is purified by reverse-phase HPLC using a PHENOMENEX LUNA C18 column (21.2x250mm), 5 μm particle, eluted with a 30 min. linear gradient of 50% acetonitrile/0J% acetic acid in water to 70% acetonitrile/0J% acetic acid in water; flow rate 7.5 mL/min. and ultraviolet (UV) detection at 285 nm. The fractions containing the desired product are collected and concentrated to give 5.6 mg (53%) of product 7 as a white solid. R f = 0.29 (20% MeOH/CH 2 Cl 2 ); FAB-MS [M+Na] + Calc. 1787.5664, found 1787.5718. b) Deprotection of (7) to give desmethylvancomycin (8). The compound 7 (8J mg, 0.0046 mmol) is dissolved in 0.5 mL DMF/0.5 mL acetic acid. A small amount of palladium dichloride-bis-triphenylphosphine (~lmg) is added and the reaction vessel is filled with nitrogen. To this mixture is added, with vigorous stirring, tributyltin hydride in 100 μL portions every 5 minutes until the starting material and all intermediates disappear by TLC. The crude reaction mixture is precipitated with 30 mL acetone in a 50 mL centrifuge tube. The mixture is centrifuged and decanted to give a white solid. This white solid is dissolved in 5 mL water and kept at 4°C overnight. The next day, the suspension is filtered through a disposable 13 mm syringe filter (Whatman Inc.) and the resulting filtrate is concentrated and purified by reverse-phase HPLC using a PHENOMENEX LUNA C18 column (21.2x250mm), 5 μm particle, eluted with 0.1% trifluoroacetic acid (TFA) in water for 2 minutes and then a 30 min. linear gradient of 0.1% TFA in water to 20% acetonitrile/0J% TFA in water; flow rate of 7.5 mL/min. and ultraviolet (UN) detection at 285 nm. The fractions containing the product are combined and lyophilized to give 5.6 mg (79%) of 8 as its TFA salt as a white solid. ESI-MS [M+H] + 1434, [M+Νa] + 1456, [M-V] + 1305, [M-V-G] + 1143, ! H NMR (DMSO, 500 MHz) δ 9.45 (br d, j=3.0 Hz), 9.17 (br s), 9.06 (br s), 8.72 (br d, j=2.9 Hz), 8.56 (br d, J=5.3 Hz), 8.33 (v br s), 7.86 (s), 7.82 (m), 7.53 (d, J=9.0 Hz), 7.46 (d, J=9.5 Hz), 7.33 (d, J=8.5 Hz), 7.23 (d, J=9.0 Hz), 7.16 (s), 7.12 (v br s), 6.79 (br d, J=9.5 Hz), 6.72 (dd, J=8.5, 2.5 Hz), 6.45 (v br s), 6.41 (d, J=2.0 Hz), 6.26 (br s), 5.97 (d, j=7.0 Hz), 5.94 (br d, j=2.8 Hz), 5.78 (d, j=8.0 Hz), 5.68 (br s), 5.37 (t, j=7.5 Hz), 5.34 (br s), 5.17 (br m), 5.12 (br m), 4.90 (br s), 4.58 (q, J=6.3 Hz), 4.45 (d, J=6.0 Hz), 4.19 (br m), 3.98 (v br s), 3.70 (br d, j=l 1.0 Hz), 3.59 (t, j=8.5 Hz), 3.53 (br s), 3.45 (t, j=8.5 Hz), 2.62 (br s), 2.17 (dd, j=15.5, 7.0 Hz), 1.82 (m), 1.67 (m), 1.56 (m), 1.05 (d, J=6.5 Hz), 0.93 (d, J=6.0 Hz), 0.88 (d, J=6.0 Hz). c) Desmethylvancosamine N-(4-(4-chlorophenyl)benzyl) desmethylvancomycin (9). To a solution of desmethylvancomycin (TFA salt, 4.0 mg, 0.0026 mmol) in 0.3 mL DMF is added DIEA (0.0022 mL, 0.013 mmol) followed by a solution of 4,4'- chlorobiphenylaldehyde in DMF (0.056 mL of 10 mg/mL, 0.0026 mmol). The reaction is stirred at 60°C for 30 minutes before a solution of sodium cyanoborohydride in THF (0.0077 mL of 1.0 M, 0.0077 mmol) is added. The reaction is stirred at 65°C for 2.5h, then cooled down to room temperature and poured into 10 mL of ether. The precipitate is purified by reverse-phase HPLC using a PHENOMENEX LUNA C18 column (21.2x250mm), 5 μm particle, eluted with a 30 min. linear gradient of 10% acetonitrile/0J% acetic acid in water to 60% acetonitrile/0J% acetic acid in water; flow rate of 7.5 mL/min. and ultraviolet (UV) detection at 285 nm, to give 2.7 mg of 9 as its HOAc salt as a white solid. ESI-MS [M+H] + 1634, [M+Na] + 1656, [M-V] + 1305, [M-V-G] + 1143; Η NMR (DMSO, 500 MHz) δ 9.43 (br d, J=3.0 Hz), 9.17 (br s), 9.08 (br s), 8.65 (br d, j=2.9 Hz), 8.53 (br d, J=5.3 Hz), 8.23 (v br s), 7.88 (s), 7.65 (d, J=8.5 Hz), 7.51 (d, j=8.5 Hz), 7.47 (d, J=9.0 Hz), 7.41 (br m), 7.33 (d, J=8.0 Hz), 7.30 (br m), 7J7 (s), 6.93 (v br s), 6.78 (br d, j=10.5 Hz), 6.72 (br d, J=8.5 Hz), 6.55 . (v br s), 6.40 (br s), 6.25 (br s), 5.99 (d, J=6.0 Hz), 5.78 (br s), 5.75 (d, J=8.0 Hz), 5.58 (br s), 5.30 (br m), 5.20 (br s), 5.14 (br m), 5.12 (br m), 5.11 (br s), 5.07 (br s), 4.86 (br s), 4.58 (q, j=6.3 Hz), 4.43 (d, J=6.0 Hz), 4.32 (br m), 4.20 (br m), 4J0 (v br s), 3.68 (br d, J=l 1.0 Hz), 3.59 (t, J=8.5 Hz), 3.49 (m), 3.45 (t, j=8.5 Hz), 3.43 (m), 2.34 (br s), 2J5 (dd, j=15.5, 6.5 Hz), 1.91 (s), 1.72 (m), 1.50 (m), 1.44 (m), 1.07 (d, j=6.5 Hz), 0.90 (d, j=6.0 Hz), 0.86 (d, j=6.0 Hz). EXAMPLE 3: Preparation of Compound (5) (a) Allyl-vancomycin-dialloc tri-O-allyl (10). Vancomycin hydrochloride (3.0 g, 2 mmol) is dissolved in 25 mL water and 25 mL dioxane. NaHCO (554 mg, 6.6 mmol) in 10 mL water is added to the reaction solution followed by N-(allyloxy carbonyloxy) succinimide (2 g, 8 mmol) in 10 mL dioxane. The reaction is stirred at room temperature for 3 hours and then poured into 1000 mL acetone. The white suspension is divided into 4 centrifuge tubes and centrifuged at 4000 rps for 5 minutes. The precipitate is collected and combined to give 3.8 g of vancomycin dialloc as white solid. Part of this white solid (2.7g) is subjected to next reaction without further purification. R f 0.4 (CHCl 3 /MeOH/H 2 O=3/2/0.5). The crude vancomycin dialloc (2.7g) from the preceding reaction is dissolved in 10 mL DMF and stirred at room temperature. Ground KHCO (284 mg, 2.84 mmol) is added to the reaction solution. The suspension is stirred at reduced pressure for 30 minutes and then allyl bromide (175 μL, 2.02 mmol) is added. The reaction is stirred for 5 hours and poured into a mixture of 200 mL acetone and 800 mL ethyl ether. This white suspension is divided into 4 centrifuge tubes and centrifuged at 5000 rps for 15 minutes. The precipitate is collected and dried to give 3 g crude vancomycin dialloc allyl ester. This crude material is subjected to the next reaction without further purification. To a solution of vancomycin dialloc allyl ester (assume 100% from last reaction) in 15 mL DMF is added Cs 2 CO 3 (2.3 g, 7J mmol). This suspension is stirred under reduced pressure for 15 minutes and then allyl bromide (1.3 mL, 14.2 mmol) is added. The reaction is stirred at room temperature overnight until TLC indicates that the reaction is complete. The suspension is precipitated with 200 mL water. The white suspension is divided into 4 centrifuge tubes and centrifuged at 5000 rps for 60 minutes. The precipitate is collected and loaded onto a silica gel column (50mmxl5cm) and eluted with 5% MeOH/CHCl (200 mL) and then 20% MeOH/CHCl 3 (500 mL) to give 2 g (82%, 3 steps) compound 10 as white solid. R f 0.65 (20% MeOH/CHCl 3 ); HR-MS(FAB+) calcd for C 86 H 99 N 9 O 28 Cl 2 Na [M+Na + ]: 1798.5874, found 1798.5844. (b) Allyl dialloc tri-OAll peracetylated vancomycin (11). To a solution of compound 10 (100 mg, 0.0563 mmol) in 5 mL CH2CI2 is added DMAP (2 mg) and pyridine (164 μL, 2.02 mmol) and acetic anhydride (96 μL, 1.01 mmol). The reaction is stirred at room temperature for 5 hours and then quenched with 0.5 mL methanol. The solution is concentrated under vacuum and the residue is loaded onto a silica gel column (30mmxl0cm) and eluted with 5% MeOH/CHCl 3 to give 104 mg (91%) of compound 11 as white solid. R f 0.2 (5% MeOH/CHCl 3 ); HR-MS calcd for C 98 H,,ιN 9 O 34 Cl 2 Na [M+Na + ]: 2050.6508, found 2050.6458. (c) Pseudoaglycone from degradation (5). To a solution of compound 11 (135 mg, 0.0666 mmol) in 6 mL CH2CI 2 is added PhSH (68 μL, 0.666 mmol) and BF 3 Et 2 O (246 μL, 2 mmol). The reaction is stirred at room temperature for 25 minutes. The reaction is loaded directly onto a silica gel column(30mmxl0cm) and eluted with 50 mL CHC1 3 , then with 5% MeOH/CHCl 3 to give 98mg (84%) of compound 5 as white solid. R f 0.23 (5% MeOH/CHCl 3 ); HR-MS calcd for C 85 H 92 N 8 O 29 Cl 2 Na [M+Na + ]: 1781.5245, found 1781.5317; 1H NMR: EXAMPLE 4: Preparation of Compound (1) The steps in preparation of compound (1) are outlined below: (a) 1 ,4-Di-O-acetyl-3-azido-2,3,6-trideoxy-α,β-L-glucopyranoside (12). To a solution of 4-O-acetyl-3-azido-2,3,6-trideoxy-α,β-L-glucopyranoside (J. Carbohyd. Chem., 1990, 9:873; J.C.S. Chem. Commun. 1987, 1171) (350 mg, 1.63 mmol) in 16 mL of CH 2 C1 2 at room temperature are added acetic anhydride (307 μL, 332 mg, 3.25 mmol), pyridine (526 μL, 515 mg, 6.51 mmol), and 4-dimethylaminopryridine (20 mg, 0.163 mmol). The reaction is stirred at room temperature for 40 min and then poured into saturated NaHCO 3 solution (20 mL). The organic and aqueous layers are separated, and the organic layer is washed with IN HC1 (20 mL) and saturated NaHCO 3 solution (20 mL), dried over Na 2 SO 4 , filtered, and concentrated to afford a yellow oil. Purification is accomplished by flash chromatography (20% EtO Ac/petroleum ether) to yield 418 mg (100%) of the product 12 as a clear oil: R f 0.57 (40% EtOAc/petroleum ether). Η NMR (CDC1 3 , 270 MHz) (« anomer) δ 6.13 (d, J= 2.6 Hz, IH, H-l), 4.70 (app t, J= 9.9 Hz, IH, H-4), 3.88 -3.78 (m, 2H, H-3 and H-5), 2.19 - 2.13 (m, IH, H-2), 2.11 (s, 3H, COCH 3 ), 2.09 (s, 3H, COCH 3 ), 1.88 - 1.77 (m, IH, H-2'), 1.14 (d, J= 5.9 Hz, 3H, H-6); 13 C NMR (CDCI3, 67.9 MHz) (α anomer) δ 169.9, 169.2, 90.6, 75.1, 68.5, 57.4, 34.2, 21.2, 20.9, 17.6; HRMS: Calculated for C 10 H, 9 N 4 O 5 (MNH 4 + ): 275.1355; Found: 275.1357 (b) Phenyl 4-O-acetyl-3-azido-2,3,6-trideoxy-l -thio-α,β-L-glucopyranoside (13). To a solution of l,4-di-O-acetyl-3-azido-2,3,6-trideoxy-α, β-L-glucopyranoside 12 (410 mg, 1.59 mmol) in 16 mL of CH 2 C1 2 at -78°C are added thiophenol (200 μL, 215 g, 1.98 mmol) and boron trifluoride diethyl etherate (1.0 mL, 1J5 g, 8J3 mmol). The reaction is stirred at - 78°C and is allowed to warm to -70°C over 1 h. The reaction mixture is poured into saturated NaHCO 3 solution (20 mL). The organic and aqueous layers are separated, and the organic layer is washed once more with saturated NaHCO 3 solution (20 mL). The aqueous layers are combined and extracted with CH 2 C1 2 (2 x 20 mL). The organic layers are combined and dried over Na 2 SO , filtered, and concentrated to give a yellow oil. Purification is accomplished by flash chromatography (10% EtO Ac/petroleum ether) to afford both α and β anomers of the product 13 (490 mg total, 100%; α:β, 3:1): R (α anomer) 0.55, R f (β anomer) 0.45 (20% EtO Ac/petroleum ether). Η NMR (CDC1 3 , 270 MHz) (oc anomer) δ 7.46 - 7.25(m, 5H, ArH), 5.57 (d, J = 5.3 Viz, IH, H-1), 4.72 (app t, J = 9.9 Hz, IH, H-4), 4.31 (qd, J= 9.6, 6.3 Hz, IH, H-5), 3.88 (ddd, J= 12.5, 9.6, 4.9 Hz, IH, H-3), 2.36 (dd, J = 13.2, 5.3 Hz, IH, H-2), 2J7 - 2.06 (m, IH, H-2'), 2J4 (s, 3H, COCH 3 ), 1.17 (d, J = 5.9 Hz, 3H, H-6); ,3 C NMR (CDC1 3 , 67.9 MHz) (α anomer) δ 170.0, 134.2, 131.3. 129J, 127.5, 83J, 75.7, 66.9, 58.4, 36J, 20.9, 17.4; HRMS: Calc'd for C, 2 Hi 9 N 4 O 2 S (MNH 4 + ): 325.1334; Found: 325.1322 (c) Phenyl 3-azido-2,3,6-trideoxy-l-thio-α,β-L-glucopyranoside (14). To a solution of phenyl-4-O-acetyl-3-azido-2,3,6-trideoxy-l-thio-α,β-L-glucopyranoside 13 (276 mg, 0.898 mmol) in 9 mL of methanol at room temperature is added potassium carbonate (74 mg, 0.449 mmol). The reaction is stirred at room temperature for 12 h. The reaction mixture is then poured into saturated NH 4 C1 (10 mL) solution. The organic and aqueous layers are separated, and the aqueous layer is extracted with CH 2 C1 2 (2 x 5 mL). The organic layers are combined, washed with saturated NH 4 C1 solution (10 mL), saturated NaHCΟ 3 solution (10 mL), and saturated NaCl solution (10 mL), dried over Na 2 SO , filtered and concentrated. Purification is accomplished by flash chromatography (gradient elution with 10-20% EtO Ac/petroleum ether) to afford 235 mg of the product 14 as a white solid: Rf 0.45 (20% EtO Ac/petroleum ether). Η NMR (CDC1 3 , 270 MHz) (α anomer) δ 7.47 - 7.27 (m, 5H ArH), 5.58 (d, J= 5.3 Hz, IH, H-1), 4.21 (qd, J= 9.2, 6.6 Hz, IH, H-5), 3.77 (ddd, J = 12.7, 9.4, 4.8 Hz, IH, H-3), 3.20 (app t, -/ = 9.2 Hz, IH, H-4), 2.39 (dd, J = 13.5, 5.0 Hz, IH, H-2), 2.26 (bs, IH, OH), 2J3 (app dt, J = 13.0, 5.7 Hz, IH, H-2'), 1.30 (d, J = 6.6 Viz, 3H, H-6); ,3 C NMR (CDC1 3 , 67.9 MHz) (α anomer) δ 134.4, 131.5, 129.0, 127.4, 83.4, 76.4, 68.8, 61.1, 36.0, 17.7; HRMS: Calc'd for C 12 H 19 N 4 O 2 S (MNH +): 283.1229; Found: 283.1233 (d) Phenyl 3-azido-2,3,6-trideoxy-l-thio-α-L-galactopyranoside (1). To a solution of phenyl 3-azido-2,3,6-trideoxy-l-thio-α,β-L-glucopyranoside 14 (231 mg, 0.871 mmol) in 9 mL of CH2CI2 at -25°C (ethanol/wet ice/dry ice) is added triflic anhydride (293 μL, 491 mg, 1.74 mmol) dropwise and pyridine (155 μL, 152 mg, 1.92 mmol). The reaction is stirred for 4 h between -25°Cand -5°C (temperature of cold bath is not stable). More Tf 2 O (200 μL, 335 mg, 1.19 mmol) and pyridine (100 μL, 97.8 mg, 1.24 mmol) are added, and the reaction is allowed to proceed for 1 h more. The reaction mixture is poured into saturated NaHCO 3 solution (10 mL). The organic and aqueous layers are separated, and the aqueous layer is extracted with CH 2 C1 2 (3 x 5 mL). The organic layers are combined and washed with IN HC1 (10 mL) and saturated NaHCO 3 (10 mL), dried over Na 2 SO 4 , filtered, and concentrated. Purification is accomplished by flash chromatography (7% EtO Ac/petroleum ether) to afford 190 mg (71% yield) of the desired product 15: R 0.69 (20% EtO Ac/petroleum ether). To a solution of phenyl 3-azido-2,3,6-trideoxy-l-thio-4-O-trifloyl-α-L-glucopyranoside 15 (190 mg, 0.616 mmol) in dimethylformamide (6.2 mL) at room temperature are added potassium benzoate (118 mg, 0.739 mmol) and 18-crown-6 (195 mg, 0.739 mmol). The reaction appears to be complete after 1 hour, but is stirred overnight (15 h) at room temperature. The reaction mixture is diluted with 10 mL of EtO Ac and poured into saturated NaHCO solution (10 mL). The organic and aqueous layers are separated, and the aqueous layer is extracted with EtOAc (2 x 5 mL). The organic layers are combined, washed with saturated NaHCO 3 solution (10 mL) and saturated NaCl solution (10 mL), dried over Na 2 SO 4 , filtered, and concentrated: R/O.62 (20% EtOAc/petroleum ether). To a solution of phenyl 3-azido-2,3,6-trideoxy-l-thio-4-O-benzoyl-α-L-galactopyranoside (228 mg, 0.616 mmol, theoretical yield from previous reaction) in 6 mL of methanol at room temperature is added lithium hydroxide monohydrate (259 mg, 6J6 mmol). The reaction. is stirred at room temperature for 18 h. The reaction mixture is diluted with 10 mL of EtO Ac and poured into saturated NH 4 C1 solution. The organic and aqueous layers are separated, and the organic layer is washed with saturated NaHCO 3 solution (5 mL) and saturated NaCl solution (5 mL), dried over Na 2 SO 4 , filtered, and concentrated. The crude product is purified by flash chromatography (2% MeOH/CH Cl 2 ) to afford 91 mg (55%, 2 steps) of the desired product la: R/0.33 (20% EtOAc/petroleum ether). The β anomer of this product is prepared in exactly the same way; spectroscopic data for this compound are identical to those given for lb. Η NMR (CDC1 3 , 270 MHz) (α anomer) δ 7.51 - 7.23 (m, 5H ArH), 5.70 (d, J= 5.9 Hz, IH, H-1), 4.42 (q, J= 6.6 Viz, IH, H-5), 3.81 - 3.75 (m, 2H, H-3 and H-4), 2.48 (app dt, J = 13.4, 5.7 Hz, IH, H-2), 2.1 1 (dd, J = 14.1, 3.5 Hz, IH, H-2'), 1.97 (bs, IH, OH), 1.28 (d, J = 6.6 Hz, 3H, H-6); 13 C NMR (CDC1 3 , 67.9 MHZ) (α anomer) δ 134.6, 131.4, 129.2, 127.5, 83.7, 70.0, 67.2, 57.9, 29,7, 16.9; HRMS: Calc'd for C, 2 H, 9 N 4 O 2 S (MNH 4 +): 283.1229; Found: 283.1221 EXAMPLE 5: Biological Testing Compounds are tested for their effect on peptidoglycan synthesis in ether-treated bacteria prepared from E. coli W7 in parallel reactions. One reaction is run in the presence of penicillin G (1 mg/mL). The product of this reaction is "immature" peptidoglycan, a polysaccharide chain with peptide side groups, but with no peptide cross-links between polysaccharide chains. Immature peptidoglycan is soluble in 4% SDS heated to 95°C. In the second reaction, which is run without penicillin, the product is cross-linked, "mature" peptidoglycan that is insoluble in hot SDS. Both types of reactions are terminated by the addition of 6M pyridinium acetate, pH 4.2, and n-butanol (1 :4). The residue from the reaction run in the presence of penicillin G is dispersed in DMSO by sonication and filtered through a hydrophilic PVDF filter that is subsequently washed with 0.4M NH OAc prepared in methanol. The residue from the reaction run in the absence of penicillin G is suspended in 4% SDS and heated at 95°C for 15 minutes. Hot SDS-insoluble material is collected on a mixed cellulose HAWP filter that is then washed with distilled water. The series of reactions observed is summarized below. (i) Stage II steps, Translocase and Transferase: products soluble in butanol. Reactions are resistant to penicillin G. Lipid intermediate I consists of bactoprenol MurNAc- pentapeptide. Lipid intermediate II consists of bactoprenol-GlcNAc-MurNAc-pentapeptide. ETB + UDP-MurNAc-pentapeptide -> UMP + Lipid Intermediate I Lipid Intermediate I + UDP-[ I4 C]GlcNAc → UDP + [ 14 C]-Lipid Intermediate II (ii) Transglycosylase step: product retained by PVDF filter Reaction run in the presence of 1 mg/mL penicillin G to inhibit transpeptidation [' C]-Lipid Intermediate II + cell wall acceptor — » "immature" [ 14 C]-peptidoglycan (iii) Transpeptidation step: product insoluble in hot 4% SDS Reaction goes to completion (no penicillin present) [ 14 C] -peptidoglycan + [ l4 C]-peptidoglycan - cross-linked [ 14 C] -peptidoglycan Incorporation into three fractions is measured: (1) butanol-soluble radioactivity; (2) radioactivity retained by hydrophilic PVDF filters from the reaction run in the presence of 1 mg/mL penicillin G; and (3) hot SDS-insoluble radioactivity retained by mixed cellulose HAWP membrane filters from the reaction run in the absence of penicillin G. Since peptidoglycan synthesis occurs sequentially, the site of inhibition can be determined by the pattern of inhibition, as shown in the following table: In the example shown below, ramoplanin is an inhibitor of the transferase step in stage II. The compound inhibits incorporation into all three fractions. Bambermycin is the only known inhibitor of the transglycosylase step and it inhibits incorporation into the material retained by the PVDF filters and into the fraction that is insoluble in hot SDS but not into the butanol-soluble fractions. Cefoxitin inhibits transpeptidation. It only inhibits incorporation of [ rl I 4 4 ,C]GlcNAc into the hot SDS-insoluble fraction. Compound 9 is tested for activity in ether-treated bacteria (ETB) prepared from E. coli W7. Vancomycin, N-4-(4-chlorophenyl)benzylvancosamine vancomycin, and compound 8 are also tested for activity. The results are presented in Figures 2 A and 2B. Compounds 8 and 9 display inhibition of peptidoglycan synthesis. Compound 9 displays inhibition at lower levels than vancomycin. Moreover, compound 9 appears to function as a direct transglycosylase inhibitor, unlike vancomycin. The preceding Examples are intended to describe certain preferred embodiments of the present invention. It should be appreciated, however, that obvious additions and modifications of the invention will be apparent to one skilled in the art. The invention is not limited except as set forth in the claims. REFERENCES CITED Beauregard, D.A. et al. (1995), "Dimerization and Membrane Anchors in Extracellular Targeting of Vancomycin Group Antibiotics," Antimicrob. Agents Chemother., 39:781-785. Cohen M. (1992), Science, 257: 1050 Neu H. (1992). Science, 257: 1064. Axelsen, P.H. et al. (1997), J. Am. Chem. Soc. {JACS), 119:1516. Milewski, W.M. et al. (1996) "Overproduction of a 37-Kilodalton Cytoplasmic Protein Homologous to NAD+-Linked D-Lactate Dehydrogenase Associated with Vancomycin Resistance in Staphylococcus aureus," Antimicrobial Agents and Chemotherapy 40:166-172. Malabarba A., et al. (1997a), "Structural Modifications of Glycopeptide Antibiotics," Med. Res. Rev., 17(1):69-137. Nagarajan R., et al. (1988), "Selective cleavage of vancosamine, glucose, and N- methyl-leucine from vancomycin and related antibiotics," J.Chem.Soc.Chem.Comm., 1306- 1307. Nagarajan R. (1991), "Antibacterial Activities and Modes of Action of Vancomycin and Related Glycopeptides," Antimicr. Agents Chemother., 35:605-609. Nagarajan R. (1993), "Structure-activity relationships of vancomycin-type glycopeptide antibiotics," -/. Antibiotics, 46: 1 181-1 195. Prowse W., et al. (1995), Biochemistry, 34:9632-9644. Pierce C, et al. (1995), J.Chem.Soc. Perkin Trans., 2.J53-157. Williams D., et al. (1988), "Molecular Basis of the Activity of Antibiotics of the Vancomycin Group," Biochem. Pharm., 37:133-141. Walsh C. (1993), Science, 261 :308. Kannan R., et al. (1988), "Function of the Amino Sugar and N-terminal Amino Acid of the Antibiotic Vancomycin in its Complexation with Cell Wall Peptides," JACS, 110: 2946-2953. Gerhard U., et al. (1993), "The role of the sugar and chlorine substituents in the dimerization of vancomycin antibiotics," JACS, 115:232-237. Allen N. et al., (1997), "The Role of Hydrophobic Side Chains as Determinants of Antibacterial Activity of Semisynthetic Glycopeptide Antibiotics," J.Antibiot., 50: 677-684. Williams D. et al., (1993), "Toward an estimation of binding constants in aqueous solution: Studies of associations of vancomycin group antibiotics," PNAS USA, 90:1172- 1178. Williams, D.H. et al. (1998) "An Analysis of the Origins of a Cooperative Binding Energy of Dimerization," Science 280:711-714. Mackay J., et al. (1994), "Dissection of the contributions toward Dimerization of Glycopeptide Antibiotics," JACS, 1 16:4573. Thompson, L.A. and Ellman, J.A. (1996) "Synthesis and Applications of Small Molecule Libraries," Chem. Rev. 96:555-600. Gallop. M.A. et al. (1994) "Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries," J. Med. Chem. 37:1233- 1251. Gordon, E.M. et al. (1994) "Applications of Combinatorial Technologies to Drug Discovery. 2. Combinatorial Organic Synthesis, Library Screening Strategies, and Future Directions," J. Med. Chem. 37:1385-1401. Terrett, N.K. et al. (1995) "Combinatorial Synthesis - The Design of Compound Libraries and their Application to Drug Discovery," Tetrahedron 51 :8135-8173.

Claims: WHAT IS CLAIMED IS: 1. A glycopeptide of the formula A,-A 2 -A 3 -A -A 5 -A 6 -A 7 , in which each dash represents a covalent bond; wherein the group A, comprises a modified or unmodified α- amino acid residue, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl; wherein each of the groups A 2 to A comprises a modified or unmodified α-amino acid residue, whereby (i) the group A, is linked to an amino group on the group A 2 , (ii) each of the groups A 2 , A4 and A 6 bears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) the group A bears a terminal carboxyl, ester, amide, or N-substituted amide group; and wherein one or more of the groups A, to A 7 is linked via a glycosidic bond to one or more glycosidic groups each having one or more sugar residues; wherein at least one of said sugar residues bears one or more substituents of the formula YXR in which the group Y is a single bond, O, NR, or S; the group X is O, NR,, S, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR,)O, C(O)NR,, or halo (in which case Y and R are absent); and R is hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; R, is hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl: and any pharmaceutically acceptable salts thereof; provided that: X and Y are not both O; X and Y are not S and O, or O and S, respectively; and if two or more of said substituents are present, they can be the same or different; and provided that: A is linked to a glycosidic group comprising a glucose residue substituted only by hydroxyl and/or amino groups and by attachment via a glycosidic bond to wherein Z, is a single bond, NR-,, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR 4 )O, or C(O)NR4; Z 2 is a single bond, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR 5 )O, or C(O)NR 5 ; R 2 , R , R 4 and R 5 are independently hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; and wherein R is as defined above; provided that when Z 2 is SO 2 , C(O)O, C(O)S, C(S)O, C(S)S or C(NR 5 )O, then R 2 is not hydrogen. 2. The glycopeptide of claim 1 in which A 2 to A are linked sequentially by peptide bonds, and in which A2 to A are cross-linked as in a dalbaheptide. 3. The glycopeptide of claim 2 in which the glycosidic group linked to A, is a disaccharide. 4. The glycopeptide of claim 3 in which A, is a modified or unmodified α- amino acid residue, and in which A, to A 7 are linked sequentially by peptide bonds and cross- linked so as to have the structure of a dalbaheptide. 5. The glycopeptide of claim 4 in which the structures and interconnections of A, to A are those found in vancomycin. 6. The glycopeptide of claim 5 in which only A 4 is linked to a glycosidic group. 7. The glycopeptide of claim 6 in which Z 2 is a single bond and R 2 is hydrogen, alkyl, alkanoyl, aroyl or aralkanoyl. 8. The glycopeptide of claim 7 in which R 3 is hydrogen and Z, is a single bond. 9. The glycopeptide of claim 8 in which R is alkyl, aralkyl, alkanoyl, aroyl or aralkanoyl. 10. The glycopeptide of claim 9 in which the glucose residue is not substituted by an amino group. 11. The glycopeptide of claim 10 which is 12. A chemical library comprising a plurality of glycopeptides; each of said glycopeptides having the formula A,-A 2 -A -A -A 5 -A -A 7 , in which each dash represents a covalent bond; wherein the group A, comprises a modified or unmodified α-amino acid residue, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl; wherein each of the groups A 2 to A comprises a modified or unmodified α-amino acid residue, whereby (i) the group A, is linked to an amino group on the group A 2 , (ii) each of the groups A 2 , A and A 6 bears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) the group A bears a terminal carboxyl, ester, amide, or N-substituted amide group; and wherein one or more of the groups A, to A 7 is linked via a glycosidic bond to one or more glycosidic groups each having one or more sugar residues; wherein at least one of said sugar residues bears one or more substituents of the formula YXR in which the group Y is a single bond, O, NR, or S; the group X is O, NR,, S, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NRι)O, C(O)NR,, or halo (in which case Y and R are absent); and R is hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; R, is hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; and any pharmaceutically acceptable salts thereof; provided that: X and Y are not both O; X and Y are not S and O, or O and S, respectively; and if two or more of said substituents are present, they can be the same or different; and provided that: A 4 is linked to a glycosidic group comprising a glucose residue substituted only by hydroxyl and/or amino groups and by attachment via a glycosidic bond to wherein Zi is a single bond. NR-t, SO 2 , C(O)O, C(O)S, C(S)O. C(S)S, C(NR 4 )O, or C(O)NR4; Z 2 is a single bond, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR 5 )O, or C(O)NR 5 ; R2, R3, R4 and R5 are independently hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl-carbonyl. alkylsulfonyl or arylsulfonyl; and wherein R is as defined above; provided that when Z 2 is SO 2 . C(O)O, C(O)S, C(S)O, C(S)S or C(NR 5 )O, then R 2 is not hydrogen. 13. The chemical library of claim 12 in which A 2 to A are linked sequentially by peptide bonds, and in which A 2 to A 7 are cross-linked as in a dalbaheptide. 14. The chemical library of claim 13 in which the glycosidic group linked to A is a disaccharide. 15. The chemical library of claim 14 in which A, is a modified or unmodified α- amino acid residue, and in which A, to A are linked sequentially by peptide bonds and cross- linked so as to have the structure of a dalbaheptide. 16. The chemical library of claim 15 in which the structures and interconnections of A, to A are those found in vancomycin. 17. The chemical library of claim 16 in which only A 4 is linked to a glycosidic group. 18. The chemical library of claim 17 in which Z 2 is a single bond and R 2 is hydrogen, alkyl, alkanoyl, aroyl or aralkanoyl. 19. The chemical library of claim 18 in which R 3 is hydrogen and Z, is a single bond. 20. The chemical library of claim 19 in which R is alkyl, aralkyl, alkanoyl, aroyl or aralkanoyl. 21. The chemical library of claim 20 in which the glucose residue is not substituted by an amino group. 22. A method for producing the chemical library of claim 12; said method comprising at least two steps which are performed in a combinatorial format; wherein at least one of said at least two steps comprises a glycosylation reaction. 23. A glycopeptide of the formula A,-A 2 -A 3 -A -A 5 -A 6 -A , in which each dash represents a covalent bond; wherein the group A, comprises a modified or unmodified α- amino acid residue, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl; wherein each of the groups A 2 to A comprises a modified or unmodified α-amino acid residue, whereby (i) the group A, is linked to an amino group on the group A 2 , (ii) each of the groups A2, A4 and A 6 bears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) the group A bears a terminal carboxyl, ester, amide, or N-substituted amide group; and wherein one or more of the groups A, to A is linked via a glycosidic bond to one or more glycosidic groups each having one or more substituted or unsubstituted sugar residues, provided that A^ is linked to a glycosidic group comprising a glucose residue substituted only by hydroxyl and/or amino groups and by attachment via a glycosidic bond to wherein Z, is a single bond, NR,, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR,)O, or C(O)NR4; Z 2 is a single bond, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR 5 )O, or C(O)NR 5 ; R, R 2 , R 3 , R. and R 5 are independently hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; and any pharmaceutically acceptable salts thereof; provided that when Z 2 is SO 2 , C(O)O, C(O)S, C(S)O, C(S)S or C(NR 5 )O, then R 2 is not hydrogen. 24. A glycopeptide of the formula Ai^-A^A^As-A ό -A^ in which each dash represents a covalent bond; wherein the group A, comprises a modified or unmodified α- amino acid residue, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl, arylsulfonyl, guanidinyl, carbamoyl, or xanthyl; wherein each of the groups A 2 to A 7 comprises a modified or unmodified α-amino acid residue, whereby (i) the group A, is linked to an amino group on the group A 2 , (ii) each of the groups A 2 , A and A 6 bears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) the group A 7 bears a terminal carboxyl, ester, amide, or N-substituted amide group; and wherein one or more of the groups A, to A is linked via a glycosidic bond to one or more glycosidic groups each having one or more sugar residues; wherein at least one of said sugar residues bears one or more substituents of the formula YXR in which the group Y is a single bond, O, NR, or S; the group X is O, NR,, S, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR,)O, C(O)NR,, or halo (in which case Y and R are absent); and R is hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; R, is hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; and any pharmaceutically acceptable salts thereof; provided that: X and Y are not both O; X and Y are not S and O, or O and S, respectively; and if two or more of said substituents are present, they can be the same or different; and provided that: A 4 is linked to a glycosidic group comprising a glucose residue attached via a glycosidic bond to wherein Z, is a single bond, NR,, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR,)O, or C(O)NR,; Z 2 is a single bond, SO 2 , C(O)O, C(O)S, C(S)O, C(S)S, C(NR 5 )O, or C(O)NR ; R 2 , R 3 , R, and R 5 are independently hydrogen, alkyl, aryl, aralkyl, alkanoyl, aroyl, aralkanoyl, heterocyclic, heterocyclic-carbonyl, heterocyclic-alkyl-carbonyl, alkylsulfonyl or arylsulfonyl; and wherein R is as defined above; provided that when Z 2 is SO 2 , C(O)O, C(O)S, C(S)O, C(S)S or C(NR 5 )O, then R 2 is not hydrogen. 25. A process for the preparation of a carbohydrate-modified glycopeptide derivative comprising contacting a sugar having an anomeric sulfoxide substituent with a pseudoglycone or aglycone under conditions that permit a sulfoxide glycosylation reaction to take place to provide a glycopeptide having a modified carbohydrate group, the sulfoxide glycosylation reaction involving a nucleophilic group of the pseuodoglycone or aglycone, which attacks an activated anomeric sulfoxide moiety of the sugar to form a glycosidic linkage. 26. The process of claim 25 in which the sulfoxide glycosylation reaction is permitted to take place in solution. 27. The process of claim 25 in which the sulfoxide glycosylation reaction is permitted to take place over a solid phase. 28. The process of claim 25 in which the sugar comprises a monosaccharide bearing an anomeric sulfoxide substituent. 29. The process of claim 28 in which the monosaccharide is contacted with a pseudoaglycone. 30. The process of claim 25 in which the sugar comprises a disaccharide bearing an anomeric sulfoxide substituent. 31. The process of claim 30 in which the disaccharide is contacted with an aglycone. 32. The process of claim 25 in which the conditions include effective amounts of trifluoromethanesulfonic anhydride and 2,6-di-t-butylmethylpyridine. 33. The process of claim 32 in which the conditions include the presence of boron trifluoride. 34. The process of claim 25 in which the sugar having an anomeric sulfoxide substituent also bears an unhindered ester at the C-2 position. 35. The process of claim 25 in which the unhindered ester is an acetate. 36. The process of claim 34 in which the sulfoxide glycosylation reaction leads to the formation of a β glycosidic linkage. 37. The process of claim 28 in which the monosaccharide is contacted with an aglycone. 38. The process of claim 37 in which the resulting glycosylated product is subjected to a second sulfoxide glycosylation reaction involving a second sugar. 39. The process of claim 38 in which the second sugar is an azido sugar.

Inventors: KAHNE DANIEL, KAHNE, DANIEL
Applicants: UNIV PRINCETON, PRINCETON UNIVERSITY
Application year: 2000
Main classification: A61K38
IPC codes: A61K38, C07K9