Chemical Synthesis, Characterization and Biological Properties of a Novel Cyclic ADP-Ribose Analogue

Chem. J. Chinese Universities

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Chemical Synthesis, Characterization and Biological Properties of a Novel Cyclic ADP-Ribose Analogue

WANG Pei, ZHANG Yan, YANG Zhen-Jun, ZHANG Liang-Ren*, ZHANG Li-He

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China

Received:2007-06-29 Revised:1900-01-01 Online:2008-02-10 Published:2008-02-10
Contact: ZHANG Liang-Ren

Abstract

Abstract: For the investigation of the structure-activity relationship of the analogues of cyclic ADP-ribose (cADPR), a novel cyclic IDP-ribose analogue, cIDPRN, in which the northern ribose was replaced by N-carbobenzyloxy-alkylimine bridge was designed and synthesized. The enzymatic stability of cIDPRN was evaluated by the incubation with Jurkat T-lymphocytes for 0, 2 and 18 h. The result analyzed by capillary electrophoresis indicated that cIDPRN antagonized the hydrolysis, whereas cADPR was easily hydrolyzed. The Ca²⁺ signal release behavior was investigated in intact Jurkat T-lymphocytes by spectrofluorometer. It showed that cIDPRN induced calcium release either in extracellular Ca²⁺-containing or Ca²⁺-free condition. The result indicated that cIDPRN was a mild membrane-permeant agonist of cADPR/RyR signaling system. This study provided further information for understanding the effect of structure of northern ribose moiety of cIDPR on the calcium motivation activity.

Key words: Nucleotide, Analogues of cADPR, Calcium agonist, Stability

CLC Number:

O629.74

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WANG Pei, ZHANG Yan, YANG Zhen-Jun, ZHANG Liang-Ren*, ZHANG Li-He. Chemical Synthesis, Characterization and Biological Properties of a Novel Cyclic ADP-Ribose Analogue[J]. Chem. J. Chinese Universities, doi: .

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Chemical Synthesis, Characterization and Biological Properties of a Novel Cyclic ADP-Ribose Analogue

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