Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
Bioorg Med Chem Lett. 2010 Oct 1;20(19):5853-8. doi: 10.1016/j.bmcl.2010.07.106. Epub 2010 Aug 3.
Small molecules behaving as CD4 mimics were previously reported as HIV-1 entry inhibitors that block the gp120-CD4 interaction and induce a conformational change in gp120, exposing its co-receptor-binding site. A structure-activity relationship (SAR) study of a series of CD4 mimic analogs was conducted to investigate the contribution from the piperidine moiety of CD4 mimic 1 to anti-HIV activity, cytotoxicity, and CD4 mimicry effects on conformational changes of gp120. In addition, several hybrid molecules based on conjugation of a CD4 mimic analog with a selective CXCR4 antagonist were also synthesized and their utility evaluated.
小分子作为 CD4 模拟物，曾被报道为 HIV-1 进入抑制剂，可阻断 gp120-CD4 相互作用并诱导 gp120 构象变化，暴露出其共受体结合位点。对一系列 CD4 模拟物类似物进行了结构-活性关系（SAR）研究，以研究 CD4 模拟物 1 的哌啶部分对抗 HIV 活性、细胞毒性以及对 gp120 构象变化的 CD4 模拟作用的贡献。此外，还合成了基于 CD4 模拟物类似物与选择性 CXCR4 拮抗剂缀合的几种杂交分子，并对其用途进行了评估。
