Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases

被引:49
作者
Bhuiyan, MPI
Kato, T
Okauchi, T
Nishino, N [1 ]
Maeda, S
Nishino, TG
Yoshida, M
机构
[1] Kyushu Inst Technol, Grad Sch Life Sci & Syst Engn, Kitakyushu, Fukuoka 8080196, Japan
[2] Kyushu Inst Technol, Fac Engn, Kitakyushu, Fukuoka 804550, Japan
关键词
D O I
10.1016/j.bmc.2005.12.063
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A series of chlamydocin analogs with various carbonyl functionalities were designed and synthesized as histone deacetylase (HDAC) inhibitors. Chlamyclocin is a cyclic tetrapeptide containing an epoxyketone surrogate in the side chain which makes it irreversible inhibitor of HDACs, whereas apicidins are a class of cyclic tetrapeptides that contain an ethylketone moiety as zinc ligand. We replaced the epoxyketone moiety of chlamydocin with several ketones and aldehyde to synthesize potent reversible and selective HDAC inhibitors. The inhibitory activity of the cyclic tetrapeptides against histone deacetylase enzymes were evaluated and the result showed most of them are potent inhibitors. Some of them have remarkable selectivity among the HDACs. (c) 2006 Published by Elsevier Ltd.
引用
收藏
页码:3438 / 3446
页数:9
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