Recognition of HIV-inactivating peptide triazoles by the recombinant soluble Env trimer, BG505 SOSIP.664 Academic Article uri icon


MeSH Major

  • Antibodies, Viral
  • Antiviral Agents
  • HIV Envelope Protein gp120
  • HIV-1
  • Peptides
  • Triazoles


  • Peptide triazole (PT) antagonists interact with gp120 subunits of HIV-1 Env trimers to block host cell receptor interactions, trigger gp120 shedding, irreversibly inactivate virus and inhibit infection. Despite these enticing functions, understanding the structural mechanism of PT-Env trimer encounter has been limited. In this work, we combined competition interaction analysis and computational simulation to demonstrate PT binding to the recombinant soluble trimer, BG505 SOSIP.664, a stable variant that resembles native virus spikes in binding to CD4 receptor as well as known conformationally-dependent Env antibodies. Binding specificity and computational modeling fit with encounter through complementary PT pharmacophore Ile-triazolePro-Trp interaction with a 2-subsite cavity in the Env gp120 subunit of SOSIP trimer similar to that in monomeric gp120. These findings argue that PTs are able to recognize and bind a closed prefusion state of Env trimer upon HIV-1 encounter. The results provide a structural model of how PTs exert their function on virion trimeric spike protein and a platform to inform future antagonist design. Proteins 2017. © 2017 Wiley Periodicals, Inc.

publication date

  • January 2017



  • Academic Article



  • eng

PubMed Central ID

  • PMC5389922

Digital Object Identifier (DOI)

  • 10.1002/prot.25238

PubMed ID

  • 28056499

Additional Document Info