title: Discovery of macrocyclic peptides armed with a mechanism-based warhead: isoform-selective inhibition of human deacetylase SIRT2.
abstract: Designed to inhibit: by using the random nonstandard peptide integrated discovery (RaPID) system, highly potent isoform-selective inhibitors can be identified from a library of nonstandard macrocyclic peptides. These inhibitors, which contain a mechanism-based warhead residue, are active against the human deacetylase SIRT2, with IC(50) values in the low nanomolar region.
authors.affiliation: Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Morimoto
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suga
mesh_terms: D000595:Amino Acid Sequence; D003500:Cyclization; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D020033:Protein Isoforms; C474199:SIRT2 protein, human; D056565:Sirtuin 2