2007 Fiscal Year Final Research Report Summary
Development of ligands active specifically in intracellular Ca^<2+>-mobilizing second messenger system
| Project/Area Number |
17390027
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
SHUTO Satoshi Hokkaido University, Faculty of Pharmaceutical Sciences, Professor (70241346)
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| Project Period (FY) |
2005 – 2007
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| Keywords | cADPR / intracellular signal transduction / calcium / second messenger |
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| Research Abstract |
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.
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