synthesis and calcium mobilization activity of cadpr analogues which integrate nucleobase, northern and southern ribose modificationscadpr类似物的合成和钙动员活动整合nucleobase,北部和南部核糖的修改.pdf

Molecules 2012, 17, 4343-4356; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Calcium Mobilization Activity of cADPR Analogues Which Integrate Nucleobase, Northern and Southern Ribose Modifications Yue Zhou 1, Peilin Yu 1, Hongwei Jin 1, Zhenjun Yang 1, Jianbo Yue 2, Liangren Zhang 1,* 1 and Lihe Zhang 1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China 2 Department of Physiology, University of Hong Kong, Hong Kong, China * Author to whom correspondence should be addressed; E-Mail: liangren@; Tel: +86-10-8280-2567, Fax: +86-10-8280-5063. Received: 24 February 2012; in revised form: 31 March 2012 / Accepted: 5 April 2012 / Published: 10 April 2012 Abstract: 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 obv