Bridging between HDAC inhibitors and therapeutic applications

ORGN 320

Norikazu Nishino, nishino@life.kyutech.ac.jp1, Ryohei Furumai1, Satoko Maeda1, Nobuyuki Kobasi1, Akihiro Ito1, Junichi Nakagawa1, and Minoru Yoshida, yoshidam@riken.jp2. (1) Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4, Hibikino, Wakamatsu, Kitakyushu, 808-0196, Japan, (2) Chem. Genet. Lab, RIKEN, Hirosawa 2-1, Wako, Saitama, 351-0198, Japan
Ky-2 is a cyclic tetrapeptide related to the natural product, chlamydocin and has hydroxamic acid moiety to potently inhibit class I and II histone deacetylases. The cyclic peptide framework could be variously modified in order to find out any specificity in nhibition of several HDACs. Based on such a synthetic HDAC inhibitor library, we started a voyage to discover new world of appication for diseases. Prelininary application of Ky-2 to solid cancer, rheumatoid arthritis, and diabetes by animal tests provided considerable informations. In addition, for the first time, X-ray crystallografic work on tHDAC/Ky-2 co-crystal revealed the extreme conformational change including trans/cis transformaton of the peptide bond. This observation suggests us new approach in design of therapeutic agents.
 

Small Molecule Therapeutic Agents
8:30 AM-11:50 AM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- 207A, Oral

Division of Organic Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009