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

US6710168B1 · kind B1 · utility

Assignee

• The Trustees of The University of Princeton · US

Inventors

• Daniel Kahne · Brookline, US
• Robert Kerns · Iowa City, US
• Seketsu Fukuzawa · Tokyo, JP
• Min Ge · Nanjing, CN
• Christopher Thompson · Gaithersburg, US

Key dates

• Filing date: Jul 14, 1999
• Grant date: Mar 23, 2004
• Expiry date: Jul 14, 2019

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K9/008
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

A glycopeptide of the formula A1—A2—A3—A4—A5—A6—A7, in which each dash represents a covalent bond; wherein A1 comprises a modified or unmodified &agr;-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 A2 to A7 comprises a modified or unmodified &agr;-amino acid residue, whereby (i) A1 is linked to an amino group on A2, (ii) each of 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) A7 bears a terminal carboxyl, ester, amide, or N-substituted amide group;and wherein one or more of A1 to A7 is linked via a glycosidic bond to one or more glycosidic groups each having one or more sugar residues, at least one of the sugar residues bearing one or more substituents of the formula YXR, N+(R1)═CR2R3, N═PR1R2R3, N+R1R2R3 or P+R1R2R3 in which Y is a single bond, O, NR1 or S; X is O, NR1, S, SO2, C(O)O, C(O)S, C(S)O, C(S)S, C(NR1)O, C(O)NR1, or halo (in which case Y and R are abs…