作者: Shuwen Liu , Weiguo Jing , Byron Cheung , Hong Lu , Jane Sun
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摘要: T20 (Fuzeon), a novel anti-human immunodeficiency virus (HIV) drug, is peptide derived from HIV-1 gp41 C-terminal heptad repeat (CHR). Its mechanism of action has not yet been defined. We applied Pepscan strategy to determine the relationship between functional domains and mechanisms five 36-mer overlapping peptides with shift amino acids (aa): CHR-1 (aa 623–658), C36 628–663), CHR-3 633–668), 638–673), CHR-5 643–678). addition two aa N terminus C34. Peptides contain N-terminal (NHR)- pocket-binding domains. They inhibited fusion by interacting NHR, forming stable six-helix bundles blocking core formation. Peptide containing partial NHR- lipid-binding domains, but lacking domain, blocked viral binding its N- sequences NHR cell membrane, respectively. CHR-3, which located in middle T20, overlaps >86% these peptides, lacks pocket- exhibited marginal anti-HIV-1 activity. These results suggest that different through they inhibit entry distinct action. The multiple CHR their partners may serve as targets for rational design new drugs vaccines.