Planta Med 2013; 79 - PS5
DOI: 10.1055/s-0033-1348819

Fluorescence Probe of Calyculin A, the Protein Phosphatase PP1/2A inhibitor

H Tajima 1, T Wakimoto 1, P Wen 1, K Hanaoka 1, T Nagano 1, I Abe 1
  • 1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113 – 0033, Japan

Calyculin A (1), isolated from the marine sponge Discodermia calyx, exhibits potent inhibitory activity against protein phosphatases PP1 and 2A. These enzymes are ubiquitously expressed in eukaryotes and catalyze the dephosphorylation of phosphorylated Ser/Thr residue. Considering the essential roles of PP1/2A in many aspects of cellular functions, fluorescence probe specific to these enzymes would be significant, but has not been reported so far. Therefore we launched a study to develop a fluorescence probe based on the specific inhibitor, 1.

Previous studies on the structure-activity relationship of 1 revealed the essential moieties for enzyme inhibition, which allowed for the rational modification designed to retain the affinity to the enzymes. As a result, we succeeded in the synthesis of TokyoGreen-calyculin A (TGCA, 2) bearing a fluorescent group in place of terminal amino acid. The synthesis of TGCA together with its bioactivity and fluorescence imaging will be presented.

Fig. 1: PS5