Inhibitory profile of a LEDGF/p75 peptide against HIV-1 integrase: Insight into integrase–DNA complex formation and catalysis

A lens epithelium-derived growth factor (LEDGF)/p75 peptide was evaluated for human immunodeficiency virus type 1 integrase (IN) inhibitory activity. The LEDGF/p75 peptide modestly inhibited IN catalysis and was dependent on IN–DNA assembly. The peptide was also effective at disrupting LEDGF/p75–IN complex formation. We next investigated the activity of the LEDGF/p75 peptide on IN mutant proteins that are unable to catalyze the DNA strand transfer reaction. The LEDGF/p75 peptide displayed an increased potency on these IN proteins, from 5-fold to greater than 10-fold, indicating the IN multimeric state greatly influences the peptide inhibitory effects. These results shed light on IN–DNA multimeric formation, and how this process influences the LEDGF/p75–IN interaction.