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Calcium‐Mobilizing Behaviors of Neutral Cyclic ADP‐Ribose Mimics that Integrate Modifications to the Nucleobase, Northern Ribose and Pyrophosphate
Author(s) -
Wang Xuan,
Zhang Xiaoyan,
Zhang Kehui,
Hu Jianxing,
Liu Zhenming,
Jin Hongwei,
Zhang Liangren,
Zhang Lihe
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800133
Subject(s) - pyrophosphate , chemistry , moiety , ryanodine receptor , endoplasmic reticulum , ribose , biochemistry , nucleobase , stereochemistry , cyclic adp ribose , cd38 , microbiology and biotechnology , dna , enzyme , biology , stem cell , cd34
Cyclic adenosine diphosphate ribose (cADPR) is an endogenous Ca 2+ mobilizer involved in diverse cellular processes. Mimics of cADPR play a crucial role in investigating the molecular mechanism(s) of cADPR‐mediated signaling. Here, compound 3 , a mimic of cADPR in which a neutral triazole moiety and an ether linkage were introduced to substitute the pyrophosphate and “northern” ribose components, respectively, was synthesized for the first time. The pharmacological activities in Jurkat cells indicated that this mimic is capable of penetrating plasma membrane and inciting Ca 2+ release from the endoplasmic reticulum (ER) through the action of ryanodine receptors (RyRs) and triggering Ca 2+ influx. Furthermore, a uridine moiety was introduced in place of adenine and the new cADPR mimics 4 and 5 were synthesized. The results of biological investigation showed that these mimics also targeted RyRs and retained moderate Ca 2+ agonistic activities. The results indicated that the neutral cADPR mimics had the same targets for inducing Ca 2+ signaling.