Interfacial peptide inhibitors of HIV-1 integrase activity and dimerization

Bioorg Med Chem Lett. 2003 Mar 24;13(6):1175-7. doi: 10.1016/s0960-894x(03)00040-4.

Abstract

Peptides derived from the interfacial region of dimeric HIV-1 integrase were evaluated as inhibitors of integrase's 3'-endonuclease activity. Three peptides were found to be moderately potent inhibitors with IC(50) values in the low micromolar range. The mode of inhibition was probed through protein crosslinking experiments. Active interfacial peptides were found to inhibit crosslinking of the dimeric form of integrase. Interfacial peptides that were poor inhibitors had no effect on integrase crosslinking.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Cross-Linking Reagents
  • Electrophoresis, Polyacrylamide Gel
  • HIV Integrase / chemistry*
  • HIV Integrase / drug effects
  • HIV Integrase / genetics
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / pharmacology*
  • Models, Molecular
  • Mutation
  • Peptides / chemical synthesis*
  • Peptides / pharmacology*
  • Protein Denaturation

Substances

  • Cross-Linking Reagents
  • HIV Integrase Inhibitors
  • Peptides
  • HIV Integrase