Synthesis and properties of PI polyamide-SAHA conjugate
Synthesis and properties of PI polyamide-SAHA conjugate
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DOI：
10.1016/j.tetlet.2009.10.034
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发表时间：
2009-12-30
影响因子：
1.8
通讯作者：
Sugiyama, Hiroshi
中科院分区：
文献类型：
--
作者：
Ohtsuki, Akimichi;Kimura, Makoto T.;Sugiyama, Hiroshi
我们设计并合成了新型吡咯 (P)-咪唑 (1) 聚酰胺缀合物 1 和 2，其具有辛二酰苯胺异羟肟酸 (SAHA) 部分，是组蛋白脱乙酰酶 (HDAC) 的强抑制剂。 SAHA 缀合物 2 旨在靶向 p16 肿瘤抑制基因的启动子区域。使用表面等离振子共振检查 SAHA 缀合物 2 与其靶序列的 DNA 结合亲和力。使用比色测定法评估缀合物1和2的HDAC抑制活性。结果表明，尽管缀合物 2 具有相对较大的 SAHA 部分，但其在体外仍具有较高的 DNA 序列特异性结合特性和中等的 HDAC 抑制活性。研究发现 SAHA 缀合物 2 可引起 HeLa 细胞形态变化并诱导选择性组蛋白 H3 赖氨酸 9 乙酰化。 (C) 2009 Elsevier Ltd. 保留所有权利。
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.