摘要/Abstract
西夫韦肽（SFT）是一种有效抗HIV-1（Human Immunodeficiency Virus-1）融合抑制剂，它比已上市融合抑制药物T20拥有更高的药效及药代稳定性，目前已完成了Ⅱb临床实验.以西夫韦肽为模板，通过构象锁定策略将多肽中原有的盐桥替换为共价键合成了SFT订书肽SFT-1和SFT-2.产物结构经圆二光谱确认形成了α-螺旋.对所有合成多肽进行了抗HIV-1活性检测，结果表明SFT订书肽对7个HIV-1假病毒株抑制活性均高于SFT，其中SFT-1对B'亚型和B'C重组亚型病毒株抑制活性最高，SFT-2对B、CRF01_AE和CRF08_BC亚型病毒株抑制活性最高.
关键词: 西夫韦肽, HIV融合抑制剂, 构象锁定, 抗HIV-1活性
Sifuvirtide (SFT) is a potent anti-HIV-1 (human immunodeficiency virus-1) fusion inhibitor and it shows higher potency and pharmacokinetic stability than the approved fusion inhibitor T20. At present, sifuvirtide has completed the phase Ⅱb clinical trial in China. In this study, SFT-1 and SFT-2 were synthesized via all-hydrocarbon cross-linking system with replacing the original salt bridge in SFT by hydrocarbon covalent bond, using sifuvirtide as template. The anti-HIV-1 activity was evaluated for all synthetic peptides. The results indicated that SFT stapled peptides displayed high inhibitory activity against seven HIV-1 pseudovirus strains, and SFT-1 showed the highest inhibitory activity against B' and B'C subtype virus strains, SFT-2 showed the highest inhibitory activity against B, CRF01_AE and CRF08_BC subtype virus strains.
Key words: sifuvirtide, HIV-1 fusion inhibitor, hydrocarbon stapling, anti-HIV-1 activity
PDF全文下载地址:
点我下载PDF
