Synthesis and Agonist Activity of Cyclic ADP-Ribose Analogues with Substitution of the Northern Ribose by Ether or Alkane Chains

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• 作者：Jianfeng Xu ; Zhenjun Yang ; Werner Dammermann ; Liangren Zhang ; Andreas H. Guse ; Li-he Zhang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：September 7, 2006
• 年：2006
• 卷：49
• 期：18
• 页码：5501 - 5512
• 全文大小：378K
• 年卷期：v.49,no.18(September 7, 2006)
• ISSN：1520-4804

文摘

Novel analogues of cADPR with adenine as base and ether (10a) or different alkane chain (10b-d)substitutions of the northern ribose were synthesized from protected imidazole nucleoside 1 in good yields.The pharmacological activities of cyclic inosine diphosphoribose ether (cIDPRE) and the compounds (10a-d) were analyzed in intact human Jurkat T-lymphocytes. The results indicate that the analogues 10a-dpermeate the plasma membrane and are weak agonists of the cADPR/ryanodine receptor signaling systemin intact human Jurkat T cells. They are the first membrane-permeant and biologically active cADPR analoguesthat contain ether or alkane bridges instead of the northern ribose and retain adenine as its base.