富含脂多糖(lipopolysaccharide，LPS)的外膜是绝大多数革兰阴性(Gram-negative，G)菌生存必需的生物学屏障。LPS转运蛋白(lipopolysaccharide transport protein，Lpt)复合体LptDE负责LPS转运和外膜组装的最后关键一步，在G-菌中普遍存在且结构-功能较为保守，哺乳动物细胞中缺乏同源蛋白，是颇具开发前景的抗菌新靶标。近10年，LptDE蛋白三维结构的破译为基于此类"非酶"蛋白靶标的药物发现奠定了基础，首个作用于LptD的拟肽类化合物murepavadin开启了一类新作用机制的抗菌药物研究。本文将总结LptDE的分子特征、结构-功能，梳理murepavadin等新型拟肽类抗菌药物的研究进展，以期为相关研究提供参考。
Novel antibacterial drug target against Gram-negative bacteria:lipopolysaccharide transport protein LptDE and its inhibitors
The outer membrane composed predominantly of lipopolysaccharide(LPS)is an essential biological barrier for most Gram-negative(G)bacteria.Lipopolysaccharide transport protein(Lpt)complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly.The structure and function of LptDE are highly conserved in most G-bacteria but absent in mammalian cells,and thus LptDE complex is regarded as an attractive antibacterial target.In recent 10 years,the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such"non-enzyme"proteins.Murepavadin,a peptidomimetic compound,was reported to be the first compound able to target LptD,enlightening a new class of antibacterial molecules with novel mechanisms of action.This article is devoted to summarize the molecular characteristics,structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds,in order to provide references for relevant researches.
Gram-negative bacterialipopolysaccharide outer membranelipopolysaccharide transport protein complex DEnew antibacterial drug targetnovel peptidomimetic compound
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