Identification of synthetic compounds active against VRE: the role of the lipidated aminoglucose and the structure of glycopeptide binding pocket

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• 作者：Yanxing Jia ; Eduardo Gonzalez-Zamora ; Nianchun Ma ; Zuosheng Liu ; Michè ; le Bois-Choussy ; Adriano Malabarba ; Cristina Brunati and Jieping Zhu
• 关键词：Antibiotic ; Biaryl ether ; Intramolecular nucleophilic aromatic substitution (S_NAr) reaction ; Macrocycle ; Vancomycin type glycopeptide ; Vancomycin-resistant enterococci (VRE)
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2005
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：2005
• 卷：15
• 期：20
• 页码：4594-4599
• 文件大小：206 K

摘要

A modified vancomycin binding pocket (D–O–E ring) incorporating an α-hydroxy-β-amino acid at the AA4 position is designed and synthesized. Some of these compounds display potent bioactivities against both sensitive- and resistant-strains (8 μg/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.