Development of ligands active specifically in intracellular Ca^<2+>-mobilizing second messenger system

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cADPR analogues can be used in proving the mechanism of cADPR-mediated Ca^<2+> signaling pathways and are also expected to be lead structures for the development of drugs, since cADPR has been shown to play important physiological roles, such as insulin release from β-cells. We previously developed cyclic ADP-carbocyclic-ribose (cADPcR), a biologically and chemically stable mimic of cADPR. We planned to develop further effective compounds based on the structure of cADPcR, and designed the N1-unsaturated carbocyclic analogs of cADPR, 4"-branched cADPcR analogs and 4"-thio-cADPR, etc. The synthesis of the N1-unsaturated carbocyclic analog has been achieved to show that it significantly active in T cells. For the synthesis of the 4-thio analog, the key step, that is intramolecular condensation forming the large 18-membered pyrophosphate ring, has been cleared. Thus, after completion of the synthesis by the one step deprotection, its biological activity will be investigated.