Synthesis and properties of PI polyamide-SAHA conjugate

被引：44

作者：

Ohtsuki, Akimichi ^{[1
]}

Kimura, Makoto T. ^{[2
]}

Minoshima, Masafumi ^{[1
]}

Suzuki, Tsukasa ^{[2
]}

Ikeda, Maki ^{[2
]}

Bando, Toshikazu ^{[1
]}

Nagase, Hiroki ^{[2
]}

Shinohara, Ken-ichi ^{[1
]}

Sugiyama, Hiroshi ^{[1
,3
]}

机构：

[1] Kyoto Univ, Dept Chem, Grad Sch Sci, Sakyo Ku, Kyoto 6068502, Japan

[2] Nihon Univ, Div Canc Genet, Dept Adv Med Sci, Sch Med, Tokyo 1738610, Japan

[3] Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Kyoto 6068502, Japan

来源：

TETRAHEDRON LETTERS | 2009年 / 50卷 / 52期

基金：

日本学术振兴会;

关键词：

HISTONE DEACETYLASE; HAIRPIN POLYAMIDES; MINOR-GROOVE; DNA; RECOGNITION; BINDING; CANCER; DISCRIMINATION; TRANSCRIPTION; INHIBITORS;

D O I：

10.1016/j.tetlet.2009.10.034

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

We have designed and synthesized new types of pyrrole (P)-imidazole (1) polyamide conjugates 1 and 2 possessing a suberoylanilide hydroxamic acid (SAHA) moiety that is a Strong inhibitor of histone deacetylase (HDAC). SAHA conjugate 2 was designed to target the Promoter region of the p16 tumor suppressor gene. The DNA binding affinity of SAHA conjugate 2 to its target sequence was examined using surface plasmon resonance. HDAC inhibition activity of conjugates 1 and 2 was evaluated using a colorimetric assay. The results demonstrated that even though it possesses the relatively large SAHA moiety, conjugate 2 has high DNA sequence-specific binding properties and moderate HDAC inhibitory activity in vitro. SAHA conjugate 2 was found to cause morphological changes in HeLa cells and to induce selective Histone H3 lysine 9 acetylation. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：7288 / 7292

页数：5

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