| Title | Trifluoromethylated cyclic-ADP-ribose mimic: synthesis of 8-trifluoromethyl-N-1-[(5 ''-O-phosphorylethoxy)methyl]-5 '-O-phosphorylinosine-5 ',5 ''-cyclic pyrophosphate (8-CF3-cIDPRE) and its calcium release activity in T cells |
| Authors | Dong, Min Kirchberger, Tanja Huang, Xiangchen Yang, Zhen Jun Zhang, Liang Ren Guse, Andreas H. Zhang, Li He |
| Affiliation | Univ Med Ctr Hamburg Eppendorf, Calcium Signaling Grp, Ctr Med Expt, Inst Biochem & Mol Biol Cellular Signal Transduct, D-20246 Hamburg, Germany. Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. |
| Keywords | ADENOSINE-DIPHOSPHORIBOSE CADPR POTENT CA2+-MOBILIZING AGENT ORGANIC FLUORINE-COMPOUNDS CARBOCYCLIC-RIBOSE INOSINE DIPHOSPHORIBOSE 2ND-MESSENGER FUNCTION CRYSTAL-STRUCTURE N1-RIBOSE MOIETY DERIVATIVES LYMPHOCYTES |
| Issue Date | 2010 |
| Publisher | organic biomolecular chemistry |
| Citation | ORGANIC & BIOMOLECULAR CHEMISTRY.2010,8,(20),4705-4715. |
| Abstract | A convenient trifluoromethylation method was firstly applied to the synthesis of 8-CF3-purine nucleosides. On the basis of this method, new protection and deprotection strategies were developed for the successful synthesis of the trifluoromethylated cyclic-ADP-ribose mimic, 8-CF3-cIDPRE 1. Using intact, fura-2-loaded Jurkat T cells compound 1 and 2',3'-O-isopropylidene 8-CF3-cIDPRE 14 were characterized as membrane-permeant cADPR agonists. Contrary to the 8-substituted cADPR analogues that mainly act as antagonists of cADPR in cells, 8-substituted cIDPRE derivatives were shown to be Ca2+ mobilizing agonists. Here we report that even compound 1, the 8-substituted cIDPRE with the strong electron withdrawing CF3 group, behaves as an agonist in T cells. Interestingly, also the partially protected 2',3'-O-isopropylidene 8-CF3-cIDPRE activated Ca2+ signaling indicating only a minor role for the hydroxyl groups of the southern ribose of cADPR for its biological activity. To our knowledge 8-CF3-cIDPRE 1 is the first reported fluoro substituted cADPR mimic and 8-CF3-cIDPRE 1 and compound 14 are promising molecular probes for elucidating the mode of action of cADPR. |
| URI | http://hdl.handle.net/20.500.11897/156700 |
| ISSN | 1477-0520 |
| DOI | 10.1039/c0ob00090f |
| Indexed | SCI(E) EI PubMed |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |
