Interfacial peptide inhibitors of HIV-1 integrase activity and dimerization.
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.
Zhao
Lei
L
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
O'Reilly
Mary K
MK
Shultz
Michael D
MD
Chmielewski
Jean
J
D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D019427:HIV Integrase / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D008958:Models, Molecular; D009154:Mutation; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011489:Protein Denaturation
D003432:Cross-Linking Reagents; D019428:HIV Integrase Inhibitors; D010455:Peptides; D019427:HIV Integrase