Peptidic HIV integrase inhibitors derived from HIV gene products: structure-activity relationship studies.

Structure-activity relationship studies were conducted on HIV integrase (IN) inhibitory peptides which were found by the screening of an overlapping peptide library derived from HIV-1 gene products. Since these peptides located in the second helix of Vpr are considered to have an alpha-helical conformation, Glu-Lys pairs were introduced into the i and i+4 positions to increase the helicity of the lead compound possessing an octa-arginyl group. Ala-scan was also performed on the lead compound for the identification of the amino acid residues responsible for the inhibitory activity. The results indicated the importance of an alpha-helical structure for the expression of inhibitory activity, and presented a binding model of integrase and the lead compound. Copyright (c) 2010 Elsevier Ltd. All rights reserved.