Cell-penetrating, dimeric α-helical peptides: nanomolar inhibitors of HIV-1 transcription

Angew Chem Int Ed Engl. 2014 Sep 15;53(38):10086-9. doi: 10.1002/anie.201404684. Epub 2014 Jul 23.

Abstract

We constructed dimeric α-helical peptide bundles based on leucine (L) and lysine (K) residues for both efficient cell penetration and inhibition of the Tat-TAR interaction. The LK dimers can penetrate nearly quantitatively into eukaryotic cells and effectively inhibit the elongation of the TAR transcript at low nanomolar concentrations. The effective inhibition of HIV-1 replication strongly suggests that the LK dimer has strong potential as an anti-HIV-1 drug.

Keywords: HIV-1; antiviral agents; drug design; peptides; transcriptional inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / metabolism
  • Anti-HIV Agents / pharmacology*
  • Dimerization
  • Dose-Response Relationship, Drug
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • HeLa Cells
  • Humans
  • Microbial Sensitivity Tests
  • Peptides / chemistry
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Protein Structure, Secondary
  • Structure-Activity Relationship
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / virology*
  • Transcription, Genetic / drug effects*
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • Peptides