A novel membrane-permeant cADPR antagonist modified in the pyrophosphate bridge

摘要

A concise method for the formation of cyclopyrophosphate of cIDPRE as well as sulfur and selenium-substituted pyrophosphate cIDPRE analogues (Ps/1-cIDPRE, PSe/1-cIDPRE, Ps/2-cIDPRE and PSe/2-cIDPRE) was reported and one of the P_s-diastereo-isomers, Ps/1-cIDPRE-1, is a novel membrane-permeant cADPR antagonist. cADPR (Fig. 1), a metabolite of NAD ~+ , is a signaling molecule which regulates Ca~(2+) mobilization via ryanodine receptors (RyR) from intracellular stores in a wide variety of biological systems, such as sea urchin eggs, pancreatic β cells, smooth and cardiac muscles, T-lymphocytes, and cerebellar neurons.