title: Cyclic tetrapeptides with -SS- bridging between amino acid side chains for potent histone deacetylases' inhibition.
abstract: Cyclic depsipeptide FK228 with an intramolecular disulfide bond is a potent inhibitor of histone deacetylases (HDAC). FK228 is stable in blood because of its prodrug function, whose -SS- bond is reduced within the cell. Here, cyclic peptides with -SS- bridges between a variety of amino acids were synthesized and assayed for HDAC inhibition. Cyclic peptide 3, cyclo(-L-amino acid-L-amino acid-L-Val-D-Pro-), with an -SS- bridge between the first and second amino acids, was found to be a potent HDAC inhibitor. Cyclic peptide 7, cyclo(-L-amino acid-D-amino acid-L-Val-D-Pro-), with an -SS- bridge between the first and second amino acids, was also a potent HDAC inhibitor.
authors.affiliation: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, 804-8550, Japan, arai@che.kyutech.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Arai
authors.forename: Md
authors.initials: M
authors.lastname: Ashraful Hoque
authors.forename: Norikazu
authors.initials: N
authors.lastname: Nishino
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ito
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D004220:Disulfides; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; D006655:Histone Deacetylases