title: Bicyclic tetrapeptides as potent HDAC inhibitors: effect of aliphatic loop position and hydrophobicity on inhibitory activity.
abstract: Several histone deacetylase (HDAC) inhibiting bicyclic tetrapeptides have been designed and synthesized through intramolecular ring-closing metathesis (RCM) reaction and peptide cyclization. We designed bicyclic tetrapeptides based on CHAP31, trapoxin B and HC-toxin I. The HDAC inhibitory and p21 promoter assay results showed that the aliphatic loop position as well as the hydrophobicity plays an important role toward the activity of the bicyclic tetrapeptide HDAC inhibitors.
authors.affiliation: Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan; Department of Chemistry, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh. Electronic address: mnurulchem@gmail.com.
authors.forename: Md Nurul
authors.initials: MN
authors.lastname: Islam
authors.affiliation: Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan; Department of Chemistry, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh.
authors.forename: Md Shahidul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh.
authors.forename: Md Ashraful
authors.initials: MA
authors.lastname: Hoque
authors.affiliation: Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Kato
authors.affiliation: Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Nishino
authors.affiliation: Chemical Genetics Laboratory/Chemical Genomics Research Group, RIKEN Advanced Science Institute, Saitama 351-0198, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ito
authors.affiliation: Chemical Genetics Laboratory/Chemical Genomics Research Group, RIKEN Advanced Science Institute, Saitama 351-0198, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D056572:Histone Deacetylase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D010456:Peptides, Cyclic; C505396:cyclic hydroxamic acid-containing peptide 31; C067071:trapoxin B; C037654:HC toxin; D006655:Histone Deacetylases
keywords: Aliphatic loop position; Bicyclic tetrapeptides; Histone deacetylase inhibitors; Ring-closing metathesis