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

doi:10.3390/molecules17044343

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Molecules 2012, 17(4), 4343-4356; doi:10.3390/molecules17044343

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

Yue Zhou¹, Peilin Yu¹, Hongwei Jin¹, Zhenjun Yang¹, Jianbo Yue², Liangren Zhang^1,* and Lihe Zhang¹

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.

Received: 24 February 2012; in revised form: 31 March 2012 / Accepted: 5 April 2012 / Published: 10 April 2012

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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 obviously alter the agonistic activity.

Keywords: cADPR analogue; nucleotide; synthesis; calcium mobilization

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MDPI and ACS Style

Zhou, Y.; Yu, P.; Jin, H.; Yang, Z.; Yue, J.; Zhang, L.; Zhang, L. Synthesis and Calcium Mobilization Activity of cADPR Analogues Which Integrate Nucleobase, Northern and Southern Ribose Modifications. Molecules 2012, 17, 4343-4356.

AMA Style

Zhou Y, Yu P, Jin H, Yang Z, Yue J, Zhang L, Zhang L. Synthesis and Calcium Mobilization Activity of cADPR Analogues Which Integrate Nucleobase, Northern and Southern Ribose Modifications. Molecules. 2012; 17(4):4343-4356.

Chicago/Turabian Style

Zhou, Yue; Yu, Peilin; Jin, Hongwei; Yang, Zhenjun; Yue, Jianbo; Zhang, Liangren; Zhang, Lihe. 2012. "Synthesis and Calcium Mobilization Activity of cADPR Analogues Which Integrate Nucleobase, Northern and Southern Ribose Modifications." Molecules 17, no. 4: 4343-4356.

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