环肽抗生素替索巴丁全合成及构效关系研究进展

Total synthesis and structure-activity relationship of cyclic peptide antibiotic teixobactin:research advances

环肽抗生素替索巴丁(teixobactin)通过破坏革兰阳性菌的细胞壁杀灭细菌,因而耐甲氧西林金黄色葡萄球菌等很难对其产生出耐药性。众多学者对该药的构效关系进行了研究。笔者查阅国内外相关报道,从其发现、结构、全合成情况及构效关系等方面汇总后发现,替索巴丁的全合成非常困难,N端甲基修饰、酯键及非天然氨基酸allo-End等为非必要结构,1、4、5、8位氨基酸的构型对抗菌活性影响较大,3、4、9、10位氨基酸被Lys替代后能较大程度地保留抗菌能力。

Teixobactin,a cyclic-peptide antibiotic,destroys the cell walls of Gram-positive bacteria. It is therefore difficult for bacteria such as meticillin-resistant Staphylococcus aureus to develop resistance to it. Many scholars have studied the structure-activity relationship(SAR)of teixobactin. After reviewing the reports related to the discovery,structure,total synthesis and SAR of teixobactin,we found that the total synthesis of teixobactin was very difficult. The N-terminal methyl modification,ester bond and allo-End were unnecessary for the activity,the configuration of amino acids at the positions 1,4,5 and 8 could greatly influence the antibacterial activity,and the substitution of the amino acids at the 3,4,9 and 10 positions by Lys could retain the antibacterial activity.