Identification of synthetic compounds active against VRE: the role of the lipidated aminoglucose and the structure of glycopeptide binding pocket.
A modified vancomycin binding pocket (D-O-E ring) incorporating an alpha-hydroxy-beta-amino acid at the AA4 position is designed and synthesized. Some of these compounds display potent bioactivities against both sensitive- and resistant-strains (8 microg/ml against VREF). Both the lipidated aminoglucose and the structure of the 16-membered macrocycle are found to be important for the anti-VRE activities. The polyamine appendage at the C-terminal, on the other hand, improved the activity against vancomycin-sensitive strains.
Jia
Yanxing
Y
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France.
Gonzalez-Zamora
Eduardo
E
Ma
Nianchun
N
Liu
Zuosheng
Z
Bois-Choussy
Michèle
M
Malabarba
Adriano
A
Brunati
Cristina
C
Zhu
Jieping
J
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D016983:Enterococcus / Q000737:chemistry / Q000187:drug effects*; D006020:Glycopeptides / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D008055:Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D008055:Lipids