硫肽类抗生素化学半合成修饰研究进展  

Research Progress in Chemical Semi-synthetic Modification of Thiopeptide Antibiotics

作　　者：朱凤巧 王文贵 瞿旭东 王守锋 Zhu Fengqiao;Wang Wengui;Qu Xudong;Wang Shoufeng(Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials,College of Chemistry and Chemical Engineering,University of Jinan,Jinan 250022;State Key Laboratory of Microbial Metabolism,School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240)

机构地区：[1]济南大学化学化工学院,山东省氟化学化工材料重点实验室,济南250022 [2]上海交通大学生命科学技术学院,微生物代谢国家重点实验室,上海200240

出　　处：《化学学报》2022年第10期1448-1462,共15页Acta Chimica Sinica

基　　金：国家自然科学基金(No.31972850);微生物代谢国家重点实验室开放课题(No.MMLKF21-09)资助。

摘　　要：硫肽类抗生素是一类由微生物次级代谢产生、富含硫元素并且氨基酸残基被高度修饰的核糖体肽类天然产物.硫肽类抗生素具有包括抗感染、抗肿瘤和免疫抑制在内的一系列十分重要的生物活性,并且其以核糖体为靶点的作用机制与目前临床上普遍使用的抗生素均不同,这使得硫肽类抗生素发展潜力巨大,但是其水溶性差、生物利用度低等问题限制了它们在临床上的应用.为了提高硫肽类抗生素的理化性质,研究者尝试用化学半合成、组合生物合成以及前体导向突变生物合成等方法对硫肽类抗生素的结构进行修饰.硫肽类抗生素本身具有的复杂结构为其化学半合成修饰提供了众多的可修饰位点.近年来,对于硫肽类抗生素的化学半合成修饰研究发展迅速.综述了近十年通过化学半合成修饰方法获得的硫肽类抗生素类似物的研究进展.Thiopetheride antibiotics are a class of ribosomal peptides that are produced by microbial secondary metabolism,rich in sulfur,and highly modified amino acid residues.Thiopeptide antibiotics have a series of very important biological activities,including anti-infection,anti-tumor and immunosuppression,and their mechanism of action targeting ribosomes is different from those commonly used in clinical practice,which makes thiopeptide antibiotics have great development potential,but their poor water solubility and low bioavailability limit their clinical application.In order to improve the physicochemical properties of thiopeptide antibiotics,researchers tried to modified the structure of thiopeptide antibiotics by means of chemosemi-synthesis,combinatorial biosynthesis and precursors directed mutation biosynthesis.The complex structure of thiopeptide antibiotics provides many modification sites for its chemical semi-synthetic modification.In recent years,research on the chemical semi-synthetic modification of thiopeptide antibiotics has developed rapidly.In this paper,the research progress of thiopeptide antibiotic analogues obtained by chemical semi-synthetic modification in recent ten years is reviewed.

关 键 词：脱氢哌啶类硫肽类抗生素 三取代吡啶类硫肽类抗生素 羟化吡啶类硫肽类抗生素 化学半合成修饰 

分 类 号：R914[医药卫生—药物化学]