title: Design and synthesis of CHAP31, trapoxin B and HC-toxin based bicyclic tetrapeptides disulfide as potent histone deacetylase inhibitors.
abstract: The naturally occurring cyclic depsipeptide, FK228 inhibits histone deacetylase (HDAC) enzymes after reductive cleavage of intra-molecular disulfide bond. One of the sulfhydryl groups produced in the reduction interacts with zinc atom that involved in the catalytic mechanism of type 1 and 2 HDACs such as HDAC1, HDAC4, and HDAC6. In the present study, we describe the development of CHAP31, trapoxin B and HC-toxin based cyclic tetrapeptides with intra-molecular disulfide bond as HDAC inhibitors. The bicyclic tetrapeptides disulfide showed potent HDAC1 and HDAC4 inhibition and p21 promoting activity.
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. Electronic address: ashraf_bio2003@yahoo.com.
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; Department of Chemistry, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh.
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.
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
keywords: Bicyclic tetrapeptides; Depsipeptide; FK228; Histone deacetylase inhibitors; Sulfhydryl group