Sulfono-γ-AA modified peptides that inhibit HIV-1 fusion

Olapeju Bolarinwa, Meng Zhang, Erin Mulry, Min Lu, Jianfeng Cai

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The utilization of bioactive peptides in the development of highly selective and potent pharmacological agents for the disruption of protein-protein interactions is appealing for drug discovery. It is known that HIV-1 entry into a host cell is through a fusion process that is mediated by the trimeric viral glycoprotein gp120/41, which is derived from gp160 through proteolytic processing. Peptides derived from the HIV gp41 C-terminus have proven to be potent in inhibiting the fusion process. These peptides bind tightly to the hydrophobic pocket on the gp-41 N-terminus, which was previously identified as a potential inhibitor binding site. In this study, we introduce modified 23-residue C-peptides, 3 and 4, bearing a sulfono-γ-AA residue substitution and hydrocarbon stapling, respectively, which were developed for HIV-1 gp-41 N-terminus binding. Intriguingly, both 3 and 4 were capable of inhibiting envelope-mediated membrane fusion in cell-cell fusion assays at nanomolar potency. Our study reveals that sulfono-γ-AA modified peptides could be used for the development of more potent anti-HIV agents.

Original languageEnglish (US)
Pages (from-to)7878-7882
Number of pages5
JournalOrganic and Biomolecular Chemistry
Volume16
Issue number42
DOIs
StatePublished - 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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