抗菌药物靶标丙氨酸消旋酶及其抑制剂研究进展

Research progress of antibacterial drug target alanine racemase and its inhibitors

摘要:

抗生素的滥用和人口的大量流动使得病原菌耐药性增强并与其他病原体产生共感染等问题，严重威胁人类的生命安全，因此，研发新型抗菌药物成为人类亟待解决的问题。丙氨酸消旋酶是以磷酸吡哆醛为辅酶催化L-丙氨酸与D-丙氨酸旋光结构互换的一类异构酶，其消旋产物D-丙氨酸对细菌细胞壁的形成具有决定性作用，与细菌性疾病密切相关。抑制丙氨酸消旋酶的活性会影响细菌的生存，近年来成为设计抗菌药物的一个理想靶位，其抑制剂的开发已成为抗菌药物研发的热点。本文从丙氨酸消旋酶的来源、结构、功能、应用及抑制剂等方面进行系统阐述，并对丙氨酸消旋酶的研究提出新的策略，为进一步研究丙氨酸消旋酶与致病菌的关系及抗菌药物候选靶标的研究提供理论基础。

Abstract:

The abuse of antibiotics and the massive migration of population make pathogenic bacteria resistant to drugs and co-infect with other pathogens, which have posed a serious threat to human life safety. Therefore, the development of new antibacterial drugs has become an urgent problem to be solved. Alanine racemase is a type of isomerases that uses pyridoxal phosphate as the coenzyme to catalyze the optical structure interchange of L-alanine and D-alanine. Its racemic product D-alanine plays a decisive role in the formation of bacterial cell wall, which is closely related to bacterial diseases. Inhibition of the activity of alanine racemase will affect the survival of bacteria. In recent years, it has become an ideal target for the design of antibacterial drugs. The development of inhibitors has become a hot topic in the research and development of antibacterial drugs. This paper systematically elaborated the source, structure, function, application and inhibitor of alanine racemase, and proposed a new strategy for the research of alanine racemase, which would provide a theoretical basis for further research on the relationship between alanine racemase and pathogenic bacteria and the candidate targets of antibacterial drugs.