Cyclic tetrapeptides with thioacetate tails or intramolecular disulfide bridge as potent inhibitors of histone deacetylases

Md Ashraful Hoque; Toru Arai; Norikazu Nishino; Hyun-Jung Kim; Akihiro Ito; Minoru Yoshida

doi:10.1016/j.bmcl.2012.03.004

Cyclic tetrapeptides with thioacetate tails or intramolecular disulfide bridge as potent inhibitors of histone deacetylases

Bioorg Med Chem Lett. 2012 Nov 1;22(21):6770-2. doi: 10.1016/j.bmcl.2012.03.004. Epub 2012 Mar 8.

Authors

Md Ashraful Hoque¹, Toru Arai, Norikazu Nishino, Hyun-Jung Kim, Akihiro Ito, Minoru Yoshida

Affiliation

¹ Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan.

PMID: 23021104
DOI: 10.1016/j.bmcl.2012.03.004

Abstract

Two thioacetate tails were introduced to the chlamydocin- and CHAP31-related cyclic tetrapeptides. An intramolecular disulfide bridge could be formed in the CHAP31-related cyclic peptides. Both the thioacetate-tailed and disulfide-bridged peptides were potent histone deacetylase inhibitors in the presence of sulfhydryl compound. Potent p21 promoter inducing activity was also observed in vivo.

MeSH terms

Chromatography, High Pressure Liquid
Disulfides / chemistry*
Histone Deacetylase Inhibitors / chemical synthesis*
Histone Deacetylase Inhibitors / chemistry
Inhibitory Concentration 50
Molecular Structure
Peptides, Cyclic / chemical synthesis*
Peptides, Cyclic / chemistry
Peptides, Cyclic / pharmacology
Sulfhydryl Compounds / chemical synthesis*
Sulfhydryl Compounds / chemistry
Sulfhydryl Compounds / pharmacology

Substances

Disulfides
Histone Deacetylase Inhibitors
Peptides, Cyclic
Sulfhydryl Compounds
thioacetic acid