Identification of a D-amino acid decapeptide HIV-1 entry inhibitor.
Identification of a D-amino acid decapeptide HIV-1 entry inhibitor.
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D-氨基酸十肽 HIV-1 进入抑制剂的鉴定。
DOI：
10.1016/j.bbrc.2006.06.150
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发表时间：
2006
影响因子：
3.1
通讯作者：
Blondelle,SylvieE
中科院分区：
文献类型：
--
作者：
Boggiano,César;Jiang,Shibo;Lu,Hong;Zhao,Qian;Liu,Shuwen;Binley,James;Blondelle,SylvieE
人类免疫缺陷病毒1型（HIV-1）病毒粒子进入宿主细胞涉及三个主要步骤，每个步骤都是开发进入抑制剂的潜在目标：gp120与CD4结合，gp120-CD4复合物与辅助受体相互作用，gp41重新折叠形成六螺旋束。利用d-氨基酸十肽组合文库，我们发现肽dC13具有强大的HIV-1融合抑制活性，并有效抑制几种实验室适应的HIV-1菌株和原代HIV-1菌株的感染。虽然dC13不阻断gp120与CD4的结合，也不破坏gp41六螺旋束的形成，但它有效地阻断了抗cxcr4单克隆抗体和趋化因子SDF-1α与表达cxcr4的细胞的结合。然而，由于使用r5的原代病毒也被中和，dC13的抗病毒活性暗示了其他的作用方式。这些结果表明dC13是一种有用的CXCR4的HIV-1共受体拮抗剂，由于其生物稳定性和简单性，可能对开发一类新的HIV-1进入抑制剂有价值。
Entry of human immunodeficiency virus type 1 (HIV-1) virion into host cells involves three major steps, each being a potential target for the development of entry inhibitors: gp120 binding to CD4, gp120-CD4 complex interacting with a coreceptor, and gp41 refolding to form a six-helix bundle. Using a d-amino acid decapeptide combinatorial library, we identified peptide dC13 as having potent HIV-1 fusion inhibitory activity, and effectively inhibiting infection by several laboratory-adapted and primary HIV-1 strains. While dC13 did not block binding of gp120 to CD4, nor disrupt the gp41 six-helix bundle formation, it effectively blocked the binding of an anti-CXCR4 monoclonal antibody and chemokine SDF-1α to CXCR4-expressing cells. However, because R5-using primary viruses were also neutralized, the antiviral activity of dC13 implies additional mode(s) of action. These results suggest that dC13 is a useful HIV-1 coreceptor antagonist for CXCR4 and, due to its biostability and simplicity, may be of value for developing a new class of HIV-1 entry inhibitors.