Design and synthesis of cyclic ADP-4-thioribose as a stable equivalent of cyclic ADP-ribose, a calcium ion-mobilizing second messenger.
Design and synthesis of cyclic ADP-4-thioribose as a stable equivalent of cyclic ADP-ribose, a calcium ion-mobilizing second messenger.
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DOI：
10.1002/anie.201302098
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发表时间：
2013-06-24
影响因子：
16.6
通讯作者：
Shuto, Satoshi
中科院分区：
文献类型：
--
作者：
Tsuzuki, Takayoshi;Sakaguchi, Natsumi;Kudoh, Takashi;Takano, Satoshi;Uehara, Masato;Murayama, Takashi;Sakurai, Takashi;Hashii, Minako;Higashida, Haruhiro;Weber, Karin;Guse, Andreas H.;Kameda, Tomoshi;Hirokawa, Takatsugu;Kumaki, Yasuhiro;Potter, Barry V. L.;Fukuda, Hayato;Arisawa, Mitsuhiro;Shuto, Satoshi
环ADP-核糖（cADPR，1，方案1），最初由Lee和同事从海胆中分离出来，[1]是细胞内Ca 2+离子信号传导的一般介质。[2]cADPR类似物已被广泛设计和合成[3，4]，因为它们在研究cADPR介导的Ca 2+释放机制和作为候选药物开发的先导结构应用方面具有潜在用途。[2]cADPR是非常不稳定的，并且不仅可以在细胞中被cADPR水解酶水解，而且可以在中性水溶液中在不稳定的N1-核糖基键处被cADPR水解。[5]我们之前合成了cADPR的模拟物cADPcR，2，其中cADPR的N1-核糖环中的氧被亚甲基取代。cADPcR在化学和生物学上都是稳定的，并且有效地动员海胆卵和神经元细胞中的细胞内Ca 2+离子。[4c]然而，cADPcR在T细胞中几乎无活性。[4d]尽管仍需要对使用cADPR的信号通路进行深入研究，但其生物学和化学不稳定性限制了对其生理作用的进一步研究。因此，需要在各种细胞（包括T细胞）中动员Ca 2+离子的cADPR的稳定类似物。我们设计了cADPR的4-硫代核糖类似物，即环ADP-4-硫代核糖（cADPtR，3），其中cADPR的N1-核糖被4-硫代核糖取代。在此，我们描述了cADPtR作为cADPR的稳定等价物的设计、合成、生物学效应和构象分析。cADPR以N6-质子化氨基形式和N6-去质子化亚氨基形式之间的平衡存在
Cyclic ADP-ribose (cADPR, 1, Scheme 1), originally isolated from sea urchins by Lee and co-workers,[1] is a general mediator of intracellular Ca2+ ion signaling.[2] Analogues of cADPR have been extensively designed and synthesized [3, 4] because of their potential usefulness for investigating the mechanisms of cADPR-mediated Ca2+ release and application as lead structures for the development of drug candidates.[2] cADPR is very unstable and can be hydrolyzed not only by cADPR hydrolase in cells but also in neutral aqueous solution at the labile N1-ribosyl linkage.[5] We previously synthesized cyclic ADP-carbocyclic-ribose (cADPcR, 2) as a stable mimic of cADPR, in which the oxygen in the N1-ribose ring of cADPR was replaced by methylene. cADPcR is both chemically and biologically stable and effectively mobilizes intracellular Ca2+ ions in sea urchin eggs and neuronal cells.[4c] However, cADPcR is almost inactive in T cells.[4d]Although intensive studies of the signaling pathway that uses cADPR are still needed, its biological and chemical instability limits further studies of its physiological role. Therefore, stable analogues of cADPR mobilizing Ca2+ ions in various cells, including T cells, are needed. We designed a 4-thioribose analogue of cADPR, that is, cyclic ADP-4-thioribose (cADPtR, 3), in which the N1-ribose of cADPR was replaced by a 4-thioribose. Herein, we describe the design, synthesis, biological effects, and conformational analysis of cADPtR as a stable equivalent of cADPR. cADPR exists in an equilibrium between the N6-protonated amino form and the N6-deprotonated imino form
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影响因子：
7.3
作者：
Moreau, Christelle;Kirchberger, Tanja;Zhang, Bo;Thomas, Mark P.;Weber, Karin;Guse, Andreas H.;Potter, Barry V. L.
通讯作者：
Potter, Barry V. L.
影响因子：
4.8
作者：
Schwarzmann, N;Kunerth, S;Guse, AH
通讯作者：
Guse, AH
DOI：
10.1152/ajpregu.00519.2001
发表时间：
2002-03-01
影响因子：
2.8
作者：
Shiwa, M;Murayama, T;Ogawa, Y
通讯作者：
Ogawa, Y
影响因子：
15
作者：
Shuto, S;Fukuoka, M;Matsuda, A
通讯作者：
Matsuda, A
影响因子：
1.3
作者：
ASSELINE, U;THUONG, NT
通讯作者：
THUONG, NT