title: Covalent Inhibition of HIV-1 Integrase by N-Succinimidyl Peptides.
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.
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.|Department of Chemistry, Midnapore College (Autonomous), Raja Bazar Main Road, Medinipur, 721101, West Bengal, India.
authors.forename: Koushik
authors.initials: K
authors.lastname: Chandra
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.
authors.forename: Priyadip
authors.initials: P
authors.lastname: Das
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.
authors.forename: Samarasimhareddy
authors.initials: S
authors.lastname: Mamidi
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.
authors.forename: Mattan
authors.initials: M
authors.lastname: Hurevich
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Iosub-Amir
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.
authors.forename: Norman
authors.initials: N
authors.lastname: Metanis
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel.
authors.forename: Meital
authors.initials: M
authors.lastname: Reches
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, 91904, Israel. assaf.friedler@mail.huji.ac.il.
authors.forename: Assaf
authors.initials: A
authors.lastname: Friedler
mesh_terms: D004305:Dose-Response Relationship, Drug; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019428:HIV Integrase Inhibitors; D010455:Peptides; D013388:Succinimides; C032620:succinimide; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: HIV-1 integrase; covalent inhibitors; peptides; succinimide