Synthesis and Calcium Mobilization Activity of cADPR Analogues Which Integrate Nucleobase, Northern and Southern Ribose Modifications

Molecules

Yue Zhou²  Peilin Yu²  Hongwei Jin²  Zhenjun Yang²  Jianbo Yue¹  Liangren Zhang² 

[1] Department of Physiology, University of Hong Kong, Hong Kong, China;State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

关键词: cADPR analogue;    nucleotide;    synthesis;    calcium mobilization;   

DOI  :  10.3390/molecules17044343

来源: mdpi

【 摘 要 】

Novel cADPR mimics, which integrate nucleobase, northern and southern ribose modifications were synthesized. The key steps of the synthesis were a Cu(I)-catalyzed Hüisgen [3+2] cycloaddition and a microwave-assisted intramolecular pyrophosphorylation. Preliminary biological investigations showed that these cADPR mimics are membrane-permeating agonists of the calcium signaling pathway. The introduction of chlorine or fluorine at the 2'-position of the southern riboses led to a decrease of activity. The existence of a hydrophobic group on the 3'-OH of the southern riboses does not obviously alter the agonistic activity.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.