Design, Synthesis, and Identification of 4″α-Azidoethyl-cyclic ADP-Carbocyclic-ribose as a Highly Potent Analogue of Cyclic ADP-Ribose, a Ca2+-Mobilizing Second Messenger

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• 作者：Takatoshi Sato ; Mizuki Watanabe ; Takayoshi Tsuzuki ; Satoshi Takano ; Takashi Murayama ; Takashi Sakurai ; Tomoshi Kameda ; Hayato Fukuda ; Mitsuhiro Arisawa ; Satoshi Shuto
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：August 11, 2016
• 年：2016
• 卷：59
• 期：15
• 页码：7282-7286
• 全文大小：346K
• 年卷期：0
• ISSN：1520-4804

文摘

Cyclic adenosine diphosphate-carbocyclic-ribose (cADPcR, 2) is a stable equivalent of cyclic adenosine diphosphate-ribose (cADPR, 1), a Ca²⁺-mobilizing second messenger. On the basis of the structure–activity relationship of cADPR-related compounds and three-dimensional structural modeling of cADPcR, we designed and synthesized cyclic-ADP-4″α-azidoethyl carbocyclic-ribose (N₃-cADPcR, 3) to demonstrate that it has a highly potent Ca²⁺-mobilizing activity (EC₅₀ = 24 nM). N₃-cADPcR will be a useful precursor for the preparation of biological tools effective to investigate cADPR-mediated signaling pathways.