Identification of a beta3-peptide HIV fusion inhibitor with improved potency in live cells

Bioorg Med Chem Lett. 2009 Jul 15;19(14):3736-8. doi: 10.1016/j.bmcl.2009.05.032. Epub 2009 May 15.

Abstract

We recently reported a beta(3)-decapeptide, betaWWI-1, that binds a validated gp41 model in vitro and inhibits gp41-mediated fusion in cell culture. Here we report six analogs of betaWWI-1 containing a variety of non-natural side chains in place of the central tryptophan of the WWI-epitope. These analogs were compared on the basis of both gp41 affinity in vitro and fusion inibition in live, HIV-infected cells. One new beta(3)-peptide, betaWXI-a, offers a significantly improved CC(50)/EC(50) ratio in the live cell assay.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • HIV Envelope Protein gp41 / metabolism
  • HIV Fusion Inhibitors / chemical synthesis
  • HIV Fusion Inhibitors / chemistry*
  • HIV Fusion Inhibitors / pharmacology
  • HIV Infections / drug therapy
  • HIV-1
  • Humans
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / pharmacology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • HIV Envelope Protein gp41
  • HIV Fusion Inhibitors
  • Peptides
  • gp41 protein, Human immunodeficiency virus 1