Chemical synthesis, characterization and biological properties of a novel cyclic ADP-ribose analogue

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.