异肽键交联的N肽类HIV-1融合抑制剂的设计、合成及活性评价  

Design,Synthesis and Activity Screening of Isopeptide Bond-tethered N Peptides as HIV-1 Fusion Inhibitors

作　　者：李雪[1] 来文庆 姜喜凤[1] 王潮[1] 刘克良[1] 

机构地区：[1]军事医学科学院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850

出　　处：《高等学校化学学报》2016年第5期881-885,共5页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:81373266,81573266)资助~~

摘　　要：报道了一种通过在HIV-1 gp41 NHR区域的多肽(N肽)之间引入异肽键稳定N3螺旋的新方法;以天然N肽序列N38为模板,采用此方法设计合成了一系列异肽键交联的N38三股α螺旋结构.该结构具有极强的热稳定性和纳摩尔水平抑制HIV-1包膜糖蛋白(Env)介导的细胞融合活性.Peptides derived from the N-terminal heptad repeat（ N-peptides） of HIV-1 gp41 can exhibit highly potent anti-HIV-1 activity when presented in a trimeric coiled-coil conformation. In this paper,the NHR trimeric coiled coils were designed based on a naturally occurring N-peptide,e.g. N38,on which engineered acyl transfer active sites were incorporated at the e/g-positions of heptad repeats to generate isopeptide bond cross-links. These isopeptide bond-tethered N-peptides exhibited exceptional thermal stability and possessed promising inhibitory activity on HIV-1 env-mediated cell-cell fusion.

关 键 词：人免疫缺陷病毒Ⅰ型 融合抑制剂 N端重复序列 卷曲螺旋 

分 类 号：O629.72[理学—有机化学]