摘要
芳基吡咯类小分子化合物NB-2衍生物(Noc或Npc)与衍生于C34中的靶标特异性多肽P26所形成的缀合物具有低纳摩尔水平的融合抑制活性.本文通过不同长度或不同柔性的连接臂将Noc或Npc与衍生于C34的靶标特异性多肽P27缀合,探讨了C34中a位残基I635和连接臂对缀合物活性的影响.人体免疫缺陷病毒1型(HIV-1)Env介导的细胞-细胞融合实验结果表明,多肽与小分子之间产生了强的协同作用.
HIV-1 fusion inhibitors target the transmembrane subunit（ gp41 ） of HIV-1 envelopeglycoproteins. Previous studies had shown that the small molecule pyrrole derivatives, Noc or Npc, can act as a substitute for the pocket binding domain of the C34 peptide, and the small molecule-peptide conjugates exhibit low nanomolar IC50 value in the cell-cell fusion assay. In this paper, pocket-specific small molecule and P27 peptide were covalenfly linked together through specified linkers with different lengths and flexibilities. Small molecule-peptide conjugates exhibited significant inhibitory activity on HIV-1 Env-mediated cell-cell fusion assay.
出处
《高等学校化学学报》
SCIE
EI
CAS
CSCD
北大核心
2014年第10期2100-2103,共4页
Chemical Journal of Chinese Universities
基金
国家自然科学基金(批准号:81373266)
'重大新药创制'科技重大专项项目(批准号:2012ZX09301003)资助~~
