EFFECTS OF HISTONE DEACETYLASE INHIBITORS BASED ON CHLAMYDOCIN TOWARD KK-A~y DIABETES MODEL MICE

摘要

Histone deacetylases (HDAC) have important roles in the regulation of the cell cycles by the cooperation with histone acetyl transferase. The HDACs involved in class-I and II have metalloprotease-related mechanism in its catalytic activity. These enzymes could be inhibited by small molecules bearing various zinc ligands such as hydroxamic acid and mercaptan. Based on the structure of chlamydocin, which has a cyclic tetrapeptide framework, cyclo(-L-Aoe-Aib-L-Phe-D-Pro-), where Aoe is (2S,9S)-2-amino-8-oxo-9,10-epoxydecanoyl, we have developed potent HDAC inhibitors.