Princeton University

Min Ge

Daniel E Kahne

Christopher Thompson

Seketsu Fukuzawa

Robert Kerns

Suzanne Walker Kahne

Peter W Park

Hongbin Men

Jeff Gildersleeve

A glycopeptide of the formula A-A-A-A-A-A-A, in which each dash represents a covalent bond; wherein Acomprises a modified or unmodified &#x3b1;-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 Ato Acomprises a modified or unmodified &#x3b1;-amino acid residue, whereby (i) Ais linked to an amino group on A, (ii) each of A, Aand Abears an aromatic side chain, which aromatic side chains are cross-linked together by two or more covalent bonds, and (iii) Abears a terminal carboxyl, ester, amide, or N-substituted amide group; A chemical library comprising a plurality of the glycopeptides of the invention. A method for preparing a glycopeptide by glycosylation of an aglycone derived from a glycopeptide antibiotic. A method for preparing a glycopeptide by preparing a pseudoaglycone from a glycopeptide antibiotic and glycosylating the pseudoaglycone.

Glycopeptide antibiotics, combinatorial libraries of glycopeptide antibiotics and methods of producing same

Methods for preparing a glycopeptide are disclosed. The methods comprise the steps of selecting a protected glycopeptide of the formula A-A-A-A-A-A-A, wherein the groups Ato Acomprise the heptapeptide structure of naturally occurring vancomycin; at least Ais linked to a glycosidic group which has a hexose residue linked to A; and the protected glycopeptide has no free amino or carboxyl groups and has a free primary hydroxyl group only at the 6-position of said hexose residue. The protected glycopeptide is contacted with a compound of the formula ArSOG where Ar is an aryl group and G is a leaving group under conditions effective to allow reaction of said free primary hydroxyl group to form a glycopeptide sulfonate ester; and the glycopeptide sulfonate ester is contacted with a nucleophile under conditions effective to allow displacement of a sulfonate group to produce a substituted glycopeptide.

Glycopeptide antibiotics, combinational libraries of glycopeptide antibiotics and methods of producing same

General methods for monitoring the activity of MurG, a GlcNAc transferase involved in bacterial cell wall biosynthesis, is disclosed. More particularly, the synthesis of simplified substrate analogs of Lipid I (the natural substrate for MurG), which function as acceptors for UDP-GlcNAc in an enzymatic reaction catalyzed by MurG, is described. Assays using the substrate analogs of the invention are further disclosed, which are useful for identifying a variety of other substrates, including inhibitors of MurG activity, for facilitating mechanistic and/or structural studies of the enzyme and for other uses. High throughput assays are also described.

Substrate analogs for MurG, methods of making same and assays using same

Substrate analogs that substitute for lipid I as a substrate for MurG

Glycosylation method

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Prineton, NJ, United States of America

Min Ge