Chemistry and biology of the ramoplanin family of peptide antibiotics
Chemistry and biology of the ramoplanin family of peptide antibiotics
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DOI：
10.1002/bip.10296
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发表时间：
2002-01-01
期刊：
影响因子：
2.9
通讯作者：
Li, WK
中科院分区：
文献类型：
--
作者：
McCafferty, DG;Cudic, P;Li, WK
肽抗生素雷莫拉宁因子 A2 是一种有前景的临床候选药物，用于治疗对糖肽、大环内酯类和青霉素等抗生素耐药的革兰氏阳性细菌感染。自 1984 年发现以来，尚未有临床或实验室对该抗生素产生耐药性的报道。雷莫拉宁的作用机制涉及肽聚糖生物合成脂质中间体的隔离，从而以物理方式阻止这些底物被后期肽聚糖生物合成酶 MurG 和转糖基酶 (TGase) 正确利用。雷莫拉宁在结构上与两种细胞壁活性脂缩肽抗生素詹尼霉素和恩尿酸丁相关，在功能上与羊毛硫抗生素类抗菌肽（美西丁、阿塔加定、乳链菌肽和表皮素）和糖肽抗生素（万古霉素和替考拉宁）成员相关。源自雷莫拉宁序列的拟肽化疗药物未来可能会用作抗生素，对抗耐万古霉素屎肠球菌 (VRE)、耐甲氧西林金黄色葡萄球菌 (MRSA) 和相关病原体。在这里，我们回顾了雷莫拉宁的化学和生物学，包括其发现、结构阐明、生物合成、抗菌活性、作用机制和全合成。 (C) 2002 年 Wiley 期刊公司
The peptide antibiotic ramoplanin factor A2 is a promising clinical candidate for treatment of Gram-positive bacterial infections that are resistant to antibiotics such as glycopeptides, macrolides, and penicillins. Since its discovery in 1984, no clinical or laboratory-generated resistance to this antibiotic has been reported. The mechanism of action of ramoplanin involves sequestration of peptidoglycan biosynthesis Lipid intermediates, thus physically occluding these substrates from proper utilization by the late-stage peptidoglycan biosynthesis enzymes MurG and the transglycosylases (TGases). Ramoplanin is structurally related to two cell wall active lipodepsipeptide antibiotics, janiemycin, and enduracidin, and is functionally related to members of the lantibiotic class of antimicrobial peptides (mersacidin, actagardine, nisin, and epidermin) and glycopeptide antibiotics (vancomycin and teicoplanin). Peptidomimetic chemotherapeutics derived from the ramoplanin sequence may find future use as antibiotics against vancomycin-resistant Enterococcus faecium (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and related pathogens. Here we review the chemistry and biology of the ramoplanins including its discovery, structure elucidation, biosynthesis, antimicrobial activity, mechanism of action, and total synthesis. (C) 2002 Wiley Periodicals, Inc.