Pavlov A Iu, Preobrazhenskaia M N
Institute for New Antibiotics, Russian Academy of Medical Sciences, Moscow, Russia.
Bioorg Khim. 1998 Sep;24(9):644-62.
New methods for the chemical modification of clinically important glycopeptide antibiotics are reviewed. Special emphasis is placed on chemical modification of the domestic antibiotic eremomycin, which has a number of advantages over the clinically used antibiotics vancomycin and teichoplanin. The most promising methods for glycopeptide modification at the aromatic ring and carboxyl group of the seventh amino acid of the peptide core and also at the amino groups of the carbohydrate moiety are discussed in detail. The structure-activity relations in a series of glycopeptide derivatives are revealed. It is shown that the presence of lipophilic substituents of certain structures and sizes is mandatory for activity toward glycopeptide-resistant enterococci to be displayed. The possibility of dimerization and interaction of these derivatives with membrane components of the bacterial cell wall is discussed. The structures of the derivatives most active toward glycopeptide-resistant enterococci and meticillin-resistant staphylococci are presented.
综述了临床重要糖肽类抗生素化学修饰的新方法。特别强调了国产抗生素埃瑞霉素的化学修饰，它比临床使用的抗生素万古霉素和替考拉宁具有许多优势。详细讨论了在肽核心第七个氨基酸的芳香环和羧基以及碳水化合物部分的氨基上进行糖肽修饰的最有前景的方法。揭示了一系列糖肽衍生物的构效关系。结果表明，具有特定结构和大小的亲脂性取代基的存在是表现出对耐糖肽肠球菌活性的必要条件。讨论了这些衍生物二聚化以及与细菌细胞壁膜成分相互作用的可能性。给出了对耐糖肽肠球菌和耐甲氧西林葡萄球菌最具活性的衍生物的结构。
