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Synthesis and properties of PI polyamide-SAHA conjugate |
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| Authors: | Akimichi Ohtsuki Masafumi Minoshima Maki Ikeda Hiroki Nagase Hiroshi Sugiyama |
| Affiliation: | a Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo, Kyoto 606-8502, Japan b Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo 173-8610, Japan c Institute for Integrated Cell-Material Sciences, Kyoto University, Sakyo, Kyoto 606-8502, Japan |
| Abstract: | We have designed and synthesized new types of pyrrole (P)-imidazole (I) 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. |
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