具有糖基转移抑制活性的抗生素研究进展

Progress in research of antibiotics as transglycosylation inhibitors

细菌细胞壁的骨架肽聚糖的生物合成过程在抗生素治疗中具有重要地位。随着细菌耐药性日益严重,糖基转移过程成为新型抗生素极有潜力的靶标。近年来,糖基转移酶的三维结构的确定,酶与抑制剂复合物结构及其相互作用的详细阐述,都为筛选和研究抑制糖基转移活性的新型抗生素提供了新的突破点。文中依照作用机制的不同,依次论述了直接抑制糖基转移酶活性的抗生素——默诺霉素及其类似物、万古霉素疏水衍生物,和作用于底物脂Ⅱ的抗生素——万古霉素和替考拉宁、雷莫拉宁、硫醚抗生素及一些推测的底物结合物,就其近年的研究进展做一综述。

Highly cross-linked peptidoglycans form a continuous covalent macromolecular net-like structure in almost all eubacteria. They are essential to bacterial life as targets for many antibiotics. The transglycosylation process becomes potential targets for new antibiotics because of the remarkable ability of bacteria to develop resistance to antibiotics. Recently, breakthrough has been achieved based on the understanding of the three-dimensional structure of the transglycosylase as well as the interaction between enzymes and inhibitors. According to different mechanisms, in this review we summarized the research progress in transglycosylase inhibitors, including moenomycin and its derivatives, hydrophobic derivatives of vancomycin, as well as agents acting on lipid Ⅱ such as vancomycin, teicoplanin, ramoplanin, lantibiotics and other presumable substrate binders.