Cyclic Adenosine 5′-Diphosphoribose (cADPR) Mimics Used as Molecular Probes in Cell Signaling

Cyclic adenosine 5′-diphosphate ribose (cADPR) is a second messenger in the Ca²⁺ signaling pathway. To elucidate its molecular mechanism in calcium release, a series of cADPR analogues with modification on ribose, nucleobase, and pyrophosphate have been investigated. Among them, the analogue with the modification of the northern ribose by ether linkage substitution (cIDPRE) exhibits membrane-permeate Ca²⁺ agonistic activity in intact HeLa cells, human T cells, mouse cardiac myocytes and neurosecretory PC12 cell lines; thus, cIDPRE and coumarin-caged cIDPRE are valuable probes to investigate the cADPR-mediated Ca²⁺ signal pathway.