Hybrids of small CD4 mimics and gp41-related peptides as dual-target HIV entry inhibitors
Hybrids of small CD4 mimics and gp41-related peptides as dual-target HIV entry inhibitors
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DOI：
10.1016/j.bmc.2022.117083
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发表时间：
2022-11-18
影响因子：
3.5
通讯作者：
Tamamura，Hirokazu
中科院分区：
文献类型：
--
作者：
Wang，Rongyi;Tsuji，Kohei;Tamamura，Hirokazu
已经开发了含有小的CD 4模拟物和gp 41-C-末端七肽重复序列（Heptad repeat，HPTR）相关肽的杂合分子。采用YIR-821衍生物作为CD 4模拟物，其抑制gp 120与CD 4的相互作用。SC-肽SC 34和SC 22 EK也被用作CHR相关肽，其抑制N-末端七肽重复序列（NHR）与NHR之间的相互作用，从而抑制膜融合。因此，这些杂合分子具有gp 120和gp 41的双重靶标。在具有不同长度接头的CD 4模拟SC肽的杂合分子的合成中，进行了两种缀合方法，Cu催化的叠氮化物-炔环加成和直接半胱氨酸烷基化。后一种反应操作简单，产率高。所合成的CD 4模拟物-SC22 EK的杂合分子具有比单独的试剂显著更高的抗HIV活性。目前的数据应该是有用的，在未来的设计抗艾滋病毒药物作为双靶点进入抑制剂。
Hybrid molecules containing small CD4 mimics and gp41-C-terminal heptad repeat (CHR)-related peptides have been developed. A YIR-821 derivative was adopted as a CD4 mimic, which inhibits the interaction of gp120 with CD4. SC-peptides, SC34 and SC22EK, were also used as CHR-related peptides, which inhibit the interaction between theN-terminal heptad repeat (NHR) and CHR and thereby membrane fusion. Therefore, these hybrid molecules have dual-targets of gp120 and gp41. In the synthesis of the hybrid molecules of CD4 mimic-SC-peptides with different lengths of linkers, two conjugating methods, Cu-catalyzed azide-alkyne cycloaddition and direct cysteine alkylation, were performed. The latter reaction caused simpler operation procedures and higher synthetic yields than the former. The synthesized hybrid molecules of CD4 mimic-SC22EK have significantly higher anti-HIV activity than each sole agent. The present data should be useful in the future design of anti-HIV agents as dual-target entry inhibitors.