Covalent Inhibition of HIV‐1 Integrase by N‐Succinimidyl Peptides. (22nd June 2016)

• Record Type: Journal Article
• Authors: Chandra, Koushik; Das, Priyadip; Mamidi, Samarasimhareddy; Hurevich, Mattan; Iosub‐Amir, Anat; Metanis, Norman; Reches, Meital; Friedler, Assaf
• Is Part Of: ChemMedChem. Volume 11:Number 18(2016)
• Page Start: 1987
• Page End: 1994
• Publication Date: 2016-06-22
• Subjects: covalent inhibitors -- HIV-1 integrase -- peptides -- succinimide; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600190
• Languages: English
• ISSNs: 1860-7179

Abstract

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. Abstract : IN the lead ! We present a new approach for the covalent inhibition of HIV‐1 integrase (IN) by direct binding of an N ‐succinimide LEDGF/p75 peptide to an amine group of a lysine residue in IN. The peptide portion serves as a specific recognition sequence for IN, whereas the succinimide acts as the binding moiety. This approach can be a promising new strategy for the design of lead compounds.