title: Peptide fibrils as monomer storage of the covalent HIV-1 integrase inhibitor.
abstract: We have recently reported the covalent inhibition of HIV-1 integrase by an N-terminal succinimide-modified lens epithelium-derived growth factor (361-370) peptide. We also showed that this peptide is proteolytically stable. Here, we show that this inhibitor is stored as fibrils that serve as a stock for the inhibitory monomers. The fibrils increase the local concentration of the peptide at the target protein. When the monomers bind integrase, the equilibrium between the fibrils and their monomers shifts towards the formation of peptide monomers. The combination of fibril formation and subsequent proteolytic stability of the peptide may bring to new strategy for developing therapeutic agents. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Institute of Chemistry and the Centre for Nanoscience and Nanotechnology, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Givat-Ram, Jerusalem, 91904, Israel.|Department of Chemistry, Midnapore College (Autonomous), Raja Bazar Main Road, Midnapore (West), 721101, West Bengal, India.
authors.forename: Koushik
authors.initials: K
authors.lastname: Chandra
authors.affiliation: Institute of Chemistry and the Centre for Nanoscience and Nanotechnology, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Givat-Ram, Jerusalem, 91904, Israel.
authors.forename: Priyadip
authors.initials: P
authors.lastname: Das
authors.affiliation: Institute of Chemistry and the Centre for Nanoscience and Nanotechnology, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Givat-Ram, Jerusalem, 91904, Israel.
authors.forename: Norman
authors.initials: N
authors.lastname: Metanis
authors.affiliation: Institute of Chemistry and the Centre for Nanoscience and Nanotechnology, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Givat-Ram, Jerusalem, 91904, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Friedler
authors.affiliation: Institute of Chemistry and the Centre for Nanoscience and Nanotechnology, Edmond J. Safra Campus, The Hebrew University of Jerusalem, Givat-Ram, Jerusalem, 91904, Israel.
authors.forename: Meital
authors.initials: M
authors.lastname: Reches
mesh_terms: D000595:Amino Acid Sequence; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry* / Q000201:enzymology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D055503:Protein Multimerization; D055550:Protein Stability; D059748:Proteolysis; D013388:Succinimides / Q000737:chemistry
chemical_list: D019428:HIV Integrase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D013388:Succinimides; C119380:lens epithelium-derived growth factor; C032620:succinimide; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: HIV-1 integrase; covalent inhibition; fibrillization; peptides; succinimide