氮唑类抗真菌药物靶酶CYP51的研究进展  

Development in research of CYP51 as the target of triazoles

作　　者：李冉[1] 张大志[1] 

机构地区：[1]第二军医大学药学院有机化学教研室,上海200433

出　　处：《药学实践杂志》2016年第2期106-109,共4页Journal of Pharmaceutical Practice

摘　　要：氮唑类药物是临床上应用最广、种类最多的广谱高效抗真菌药物,其作用靶点为真菌甾醇合成过程中的一个关键酶——羊毛甾醇14α-去甲基化酶(CYP51)。CYP51由CYP51基因(同名ERG11)表达。一方面,真菌CYP51是跨膜蛋白,难以纯化获得其准确的结构信息,成为药物研发的瓶颈之一;另一方面,CYP51变异是公认的真菌耐药的主要原因之一,研究其结构变化对于抗真菌耐药具有重要意义。因此,笔者对近年来CYP51的研究进展进行综述。Triazoles are the most widely used antifungal drugs in clinic with broad spectrum and high efficacy,which targets sterol 14α-demethylase（CYP51）,an enzyme expressed by the gene EGR11,which is a key enzyme in the fungi ergosterol biosynthesis.On the one hand,the CYP51 belongs to a transmembrane protein.It is difficult to get the exact functional structure conformation which becomes a big challenge for the development of new drugs.On the other hand,it becomes consensus that EGR11 exon mutation cause CYP51 structural change is one of the major reasons for antifungal drugs resistance.Therefore,study of the structural changes toward the antifungal drug resistance is quite important.The review authors have summarized the research progress on CYP51 over the recent years.

关 键 词：CYP51靶酶 三维结构 动力学 突变 耐药 

分 类 号：R978.5[医药卫生—药品]