环状ADP核糖 | 119340-53-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 环状ADP核糖
• 中文别名: 环二磷酸腺苷核酸糖
• 英文名称: cyclic adenosine 5'-diphosphate ribose
• 英文别名: Cyclic ADP-ribose；adenosine 5'-cyclic-diphosphoribose；cyclic adenosine 5'-diphosphoribose；cyclic adenosine diphosphate ribose；cyclic adenosine diphosphate-ribose；cyclic ADP ribose；(2R,3R,4S,5R,13R,14S,15R,16R)-8,10-dihydroxy-24-imino-8,10-dioxo-7,9,11,25,26-pentaoxa-1,17,19,22-tetraza-8λ5,10λ5-diphosphapentacyclo[18.3.1.12,5.113,16.017,21]hexacosa-18,20,22-triene-3,4,14,15-tetrol
• CAS: 119340-53-3
• 化学式: C₁₅H₂₁N₅O₁₃P₂
• 分子量: 541.305
• InChiKey: BQOHYSXSASDCEA-KEOHHSTQSA-N

物化性质

• 沸点：
  934.8±75.0 °C(Predicted)
• 密度：
  2.57±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶）、甲醇（微溶）、水（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  -5.7
• 重原子数：
  35
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  259
• 氢给体数：
  7
• 氢受体数：
  16

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 安全说明：
  S26,S36
• 储存条件：
  密封存储，在-20°C下保存。

制备方法与用途

生物活性

Cyclic ADP-ribose (cADPR) 是一种有效的钙动员第二信使，通过 ADP-核糖基环化酶从 NAD+ 合成而来。cADPR 主要通过 Ryanodine 受体介导的内质网释放以及 TRPM2 通道开放引起的细胞外流入来增加胞质钙。

靶点

• Calcium mobilization
• TRPM2 channels
• Endogenous metabolite

体外研究

• cADPR (20 nM) 能够引起海胆卵匀浆中大规模快速的 Ca²⁺ 释放。
• cADPR (100 µM; 10 min) 可以在培养的小胶质细胞中诱导出持续升高的内钙浓度（占64%）。
• cADPR (100 µM) 和加热 (35-38.5 ℃) 能刺激雄性小鼠孤立下丘脑中催产素 OT 的释放。

体内研究

• cADPR (100 µM; push-pull 类型的脑微灌注) 能够提升支配或从属小鼠中的 OT 浓度。

反应信息

• 作为反应物：
  描述：

  环状ADP核糖 在 potassium tert-butylate 、 水 作用下， 以 二甲基亚砜 为溶剂， 反应 5.0h， 以85%的产率得到phosphoribosyl-AMP
  参考文献：
  名称：

  Cyclic ADP-Ribose: Synthesis and Structural Assignment

  摘要：

  Cyclic ADP-ribose (cADPR) is a naturally occurring cyclic nucleotide and a potent mediator of calcium mobilization in many mammalian tissues. Previous studies have shown that cADPR is synthesized from beta-NAD(+) via the scission of the nicotinamide-ribose linkage and cyclization by forming a new bond between the ribose and the nitrogen of the adenine ring. However, the position and stereochemistry of this newly formed linkage were not unequivocally determined. In this study we have established that cADPR has the anomeric carbon of the ribose attached onto the N-1-nitrogen of the adenine nucleus via a beta-N-glycosyl linkage. The structural assignment was made by correlating cADPR to N-1-(5'-phosphoribosyl)AMP, a known intermediate of histidine biosynthesis. This was achieved by cleaving the pyrophosphate bond of cADPR under conditions (DMSO/tert-butoxide) not perturbing the integrity of the C-N glycosyl bond. Furthermore, cADPR was successfully synthesized by cyclization of N-1-(5'-phosphoribosyl)ATP catalyzed by NAD(+) pyrophosphorylase in an organic solvent-aqueous medium.

  DOI：

  10.1021/ja00096a002
• 作为产物：
  描述：

  β-烟酰胺腺嘌呤二核苷酸 在 sodium phosphate buffer 作用下， 反应 0.5h， 以2.5%的产率得到环状ADP核糖
  参考文献：
  名称：

  Cyclic ADP-Ribose: Synthesis and Structural Assignment

  摘要：

  Cyclic ADP-ribose (cADPR) is a naturally occurring cyclic nucleotide and a potent mediator of calcium mobilization in many mammalian tissues. Previous studies have shown that cADPR is synthesized from beta-NAD(+) via the scission of the nicotinamide-ribose linkage and cyclization by forming a new bond between the ribose and the nitrogen of the adenine ring. However, the position and stereochemistry of this newly formed linkage were not unequivocally determined. In this study we have established that cADPR has the anomeric carbon of the ribose attached onto the N-1-nitrogen of the adenine nucleus via a beta-N-glycosyl linkage. The structural assignment was made by correlating cADPR to N-1-(5'-phosphoribosyl)AMP, a known intermediate of histidine biosynthesis. This was achieved by cleaving the pyrophosphate bond of cADPR under conditions (DMSO/tert-butoxide) not perturbing the integrity of the C-N glycosyl bond. Furthermore, cADPR was successfully synthesized by cyclization of N-1-(5'-phosphoribosyl)ATP catalyzed by NAD(+) pyrophosphorylase in an organic solvent-aqueous medium.

  DOI：

  10.1021/ja00096a002

文献信息

• Chemoenzymatic synthesis of analogues of the second messenger candidate cyclic adenosine 5′-diphosphate ribose
  作者：Gloria A. Ashamu、Antony Galione、Barry V. L. Potter

  DOI：10.1039/c39950001359

  日期：——

  A broad substrate specificity for adenosine 5′-diphosphate ribosyl cyclase is demonstrated by cyclisation of ribose-and purine-modified nicotinamide adenine dinucleotide analogues to mimics of cyclic adenosine 5′-diphosphate ribose, generating a straightforward route for structural modification of this important Ca2+-mobilising nucleotide.

  通过将核糖和嘌呤修饰的烟酰胺腺嘌呤二核苷酸类似物环化为环状腺苷-5'²-二磷酸核糖的模拟物，证明了腺苷-5'²-二磷酸核糖环化酶具有广泛的底物特异性，为这种重要的钙离子动员核苷酸的结构修饰提供了一条直接途径。
• Cyclic ADP-ribose and analogs
  申请人：Wisconsin Alumni Research Foundation

  公开号：US05608047A1

  公开（公告）日：1997-03-04

  A non-enzymatic stereoselective cyclization of .beta.-NAD.sup.+ to yield cyclic ADP-ribose (cADPR). By heating .beta.-NAD.sup.+ in an anhydrous solvent in the presence of a metal halide and a nonnucleophilic base, cADPR was obtained as the sole cyclic isomer in yields as high as 28%. .alpha.-NAD was also converted into cADPR under the same reaction conditions. Several analogs of cADPR have also been synthesized and some of these analogs have a greater Ca.sup.++ release activity than cADPR itself.

  一种非酶选择性立体环化反应，将β-NAD+转化为环状ADP核糖（cADPR）。在无水溶剂中，在金属卤化物和非亲核碱的存在下加热β-NAD+，可以得到cADPR，其为唯一的环状异构体，收率高达28％。在相同的反应条件下，α-NAD也被转化为cADPR。还合成了几种cADPR的类似物，并且其中一些类似物的钙离子释放活性比cADPR本身更高。
• Cyclic ADP ribose antagonists
  申请人：Regents of the University of Minnesota

  公开号：US05486604A1

  公开（公告）日：1996-01-23

  Cyclic ADP-ribose (cADPR) analogs block cADPR from releasing Ca.sup.+2, and also inhibit cADPR from potentiating Ca.sup.+2 release induced by either divalent cations or by caffeine. 8-amino-cADPR and two other 8-substituted analogs were also synthesized. Both 8-Br- and 8-azido-cADPR were also antagonists, although with less potency than 8-amino-cADPR. These results show that alterations at the 8-position of the adenine group do not inhibit cADPR from binding to its receptor but do eliminate the ability of the metabolite to activate the Ca.sup.+2 release mechanism.

  环状腺苷酸二磷酸核糖（cADPR）类似物可以阻止cADPR释放Ca2+，并且抑制cADPR通过二价阳离子或咖啡因增强Ca2+释放的作用。8-氨基-cADPR和另外两个8-取代类似物也被合成。8-溴代和8-叠氮代-cADPR也是拮抗剂，但比8-氨基-cADPR的效力低。这些结果表明，腺嘌呤基团8位的改变不会抑制cADPR与其受体的结合，但会消除代谢物激活Ca2+释放机制的能力。
• Yamada, Shinji; Gu, Qu-Ming; Sih, Charles J., Journal of the American Chemical Society, 1994, vol. 116, # 23, p. 10787 - 10788
  作者：Yamada, Shinji、Gu, Qu-Ming、Sih, Charles J.

  DOI：——

  日期：——
• cADPR Analogues:  Effect of an Adenosine 2‘- or 3‘-Methoxy Group on Conformation
  作者：Steven M. Graham、Daniel J. Macaya、Raghuvir N. Sengupta、Kevin B. Turner

  DOI：10.1021/ol036152r

  日期：2004.1.1

  [GRAPHICS]The 2'-OMe-A (2) and 3'-OMe-A (3) analogues of the calcium release agent cADPR (1) were prepared and their solution structures studied by NMR spectroscopy. Compared to 1, 2 shows a shift in its A ring conformation and changes in its R ring N:S and gamma(t):gamma(+) ratios, while 3 displays a significant change in the conformation of its A ring gamma-bond.