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Covalent Inhibition of HIV‐1 Integrase by N ‐Succinimidyl Peptides
Author(s) -
Chandra Koushik,
Das Priyadip,
Mamidi Samarasimhareddy,
Hurevich Mattan,
IosubAmir Anat,
Metanis Norman,
Reches Meital,
Friedler Assaf
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600190
Subject(s) - succinimide , integrase , moiety , covalent bond , peptide , chemistry , residue (chemistry) , lysine , stereochemistry , combinatorial chemistry , amine gas treating , human immunodeficiency virus (hiv) , biochemistry , amino acid , biology , organic chemistry , dna , immunology
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.