Author/Authors :
Ohtsuki، نويسنده , , Akimichi and Kimura، نويسنده , , Makoto T. and Minoshima، نويسنده , , Masafumi and Suzuki، نويسنده , , Tsukasa and Ikeda، نويسنده , , Maki and Bando، نويسنده , , Toshikazu and Nagase، نويسنده , , Hiroki and Shinohara، نويسنده , , Ken-ichi and Sugiyama، نويسنده , , Hiroshi، نويسنده ,
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.
