8-amino-5'-AMP | 34051-12-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 8-amino-5'-AMP
• 英文别名: 8-aminoadenosine-5'-phosphate；8-Amino-AMP；8-amino-5'-phosphoadenosine；8-aminoadenosine 5'-monophosphate；8-amino-[5']adenylic acid；8-NH2-AMP；5'-Adenylic acid, 8-amino-；[(2R,3S,4R,5R)-5-(6,8-diaminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 34051-12-2
• 化学式: C₁₀H₁₅N₆O₇P
• 分子量: 362.239
• InChiKey: DMNZAEJUZGYJKO-UUOKFMHZSA-N

物化性质

• 沸点：
  863.1±75.0 °C(Predicted)
• 密度：
  2.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  212
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  8-amino-5'-AMP 在 2,2'-二硫二吡啶 、 NADase 、 magnesium sulfate 、 三苯基膦 、 manganese(ll) chloride 作用下， 以 formamide 、 二甲基亚砜 为溶剂， 反应 56.0h， 生成 8-Aminoadenosine 5'-diphosphoribose
  参考文献：
  名称：

  Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists

  摘要：

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.

  DOI：

  10.1021/jm401497a
• 作为产物：
  描述：

  8-azidoadenosine-5'-phosphate 在 DL-dithiothreitol 作用下， 反应 16.0h， 以65%的产率得到8-amino-5'-AMP
  参考文献：
  名称：

  Synthesis of cyclic adenosine 5′-diphosphate ribose analogues: a C2′ endo/syn “southern” ribose conformation underlies activity at the sea urchin cADPR receptor

  摘要：

  采用化学酶法合成了新型 8 取代碱基和糖修饰的 Ca2+ 调动第二信使环腺苷-5â²-二磷酸核糖（cADPR）类似物，并对其在海胆卵匀浆（SUH）和 Jurkat T 淋巴细胞中的活性进行了评估；通过 1H NMR 光谱进行的构象分析发现，C2â² 内/同步构象是 CADPR 在海胆蛋匀浆（SUH）受体（而不是在 T 细胞-CADPR 受体）中发挥激动剂或拮抗剂活性的关键。

  DOI：

  10.1039/c0ob00396d

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。
• Identification of Critical Ligand Binding Determinants in <i>Mycobacterium tuberculosis</i> Adenosine-5′-phosphosulfate Reductase
  作者：Jiyoung A. Hong、Devayani P. Bhave、Kate S. Carroll

  DOI：10.1021/jm900728u

  日期：2009.9.10

  to develop new antitubercular agents, particularly for the treatment of latent infection. To facilitate the development of potent and specific inhibitors of APS reductase, we have probed the molecular determinants that underlie binding and specificity through a series of substrate and product analogues. Our study highlights the importance of specific substitutent groups for substrate binding and provides

  结核分枝杆菌5'-磷酸腺苷 (APS) 还原酶是一种铁硫蛋白，是开发新型抗结核药物的有效靶点，特别是用于治疗潜伏感染。为了促进 APS 还原酶的强效和特异性抑制剂的开发，我们通过一系列底物和产物类似物探索了作为结合和特异性基础的分子决定因素。我们的研究强调了特定取代基团对底物结合的重要性，并为配体特异性构象状态提供了功能证据。已为结核分枝杆菌APS 还原酶开发了一个活性位点模型，该模型与此处提供的结果以及铜绿假单胞菌报告的先前结构数据一致APS 还原酶和相关酶。该模型说明了 APS 还原酶与配体相互作用所需的功能特征，并为合理设计小分子作为人类病原体（包括结核分枝杆菌）中存在的 APS 还原酶的潜在抑制剂提供了药理学路线图。
• Synthesis, Characterization, and Biological Properties of 8-Azido- and 8-Amino-Substituted 2‘,5‘-Oligoadenylates
  作者：Hiroaki Sawai、Atushi Hirano、Hiroyuki Mori、Kazuo Shinozuka、Beihua Dong、Robert H. Silverman

  DOI：10.1021/jm030035k

  日期：2003.11.1

  A series of 8-azido- and 8-amino-substituted 2',5'-oligoadenylatyes was prepared by a uranyl-ion catalyzed polymerization of the corresponding 8-substituted adenosine phosphorimidazolide. Subsequent 5'-dephosphorylation of the resulting 5'-phosphoryl 2',5'-linked oligomers with alkaline phosphatase gave the corresponding core oligomers. The CD spectra indicated that the 8-aminoadenosine analogue of the 2',5'-linked trimer has an anti-orientation as in naturally occurring 2',5'-oligoadenylates, while 8-azido-substituted 2',5'-oligoadenylates have a syn-orientation. The 8-substituted oligomers showed enhanced resistance against digestion by snake venom phosphodiesterase. The 2',5'-linked 8-azidoadenylate trimer and tetramer displayed strong RNase L binding and activating ability, although the corresponding dimer is devoid of such activities. In contrast, very low or no RNase L binding and activating ability were observed in the 8-aminoadenosine analogue of 2',5'-oligoadenylates. Results indicate that the bulkiness and ionic character of the 8-substituting group have significant effects on the ability of these analogues to bind and activate RNase L. Furthermore, the orientation of the glycosidic base in the 2-5A analogues may change from syn to anti during binding to RNase L. The 8-azidoadenosine analogues of 2-5A will be useful tools in the photoaffinity labeling of RNase L, due to their strong RNase L binding ability. In addition, these 8-azidoadenosine compounds may be considered as candidates for experimental therapeutic agents because they have enhanced stability to enzyme degradation while retaining the ability to activate RNase L.
• Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists
  作者：Christelle Moreau、Tanja Kirchberger、Joanna M. Swarbrick、Stephen J. Bartlett、Ralf Fliegert、Timur Yorgan、Andreas Bauche、Angelika Harneit、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm401497a

  日期：2013.12.27

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.
• Synthesis of cyclic adenosine 5′-diphosphate ribose analogues: a C2′ endo/syn “southern” ribose conformation underlies activity at the sea urchin cADPR receptor
  作者：Christelle Moreau、Gloria A. Ashamu、Victoria C. Bailey、Antony Galione、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1039/c0ob00396d

  日期：——

  Novel 8-substituted base and sugar-modified analogues of the Ca2+ mobilizing second messenger cyclic adenosine 5′-diphosphate ribose (cADPR) were synthesized using a chemoenzymatic approach and evaluated for activity in sea urchin egg homogenate (SUH) and in Jurkat T-lymphocytes; conformational analysis investigated by 1H NMR spectroscopy revealed that a C2′ endo/syn conformation of the “southern” ribose is crucial for agonist or antagonist activity at the SUH-, but not at the T cell-cADPR receptor.

  采用化学酶法合成了新型 8 取代碱基和糖修饰的 Ca2+ 调动第二信使环腺苷-5â²-二磷酸核糖（cADPR）类似物，并对其在海胆卵匀浆（SUH）和 Jurkat T 淋巴细胞中的活性进行了评估；通过 1H NMR 光谱进行的构象分析发现，C2â² 内/同步构象是 CADPR 在海胆蛋匀浆（SUH）受体（而不是在 T 细胞-CADPR 受体）中发挥激动剂或拮抗剂活性的关键。