Abstract:

We present a new approach for the covalent inhibition of HIV‐1 integrase (IN) by an LEDGF/p75‐derived peptide modified with an N‐terminal succinimide group. The covalent inhibition is mediated by direct binding of the succinimide to the amine group of a lysine residue in IN. The peptide serves as a specific recognition sequence for the target protein, while the succinimide serves as the binding moiety. The combination of a readily synthesizable peptide precursor with easy and efficient binding to the target protein makes this approach a promising new strategy for designing lead compounds.