adenyl(3'-5')phophoadenine | 2391-46-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （3'->5'）-二核苷酸和类似物
• 英文名称: adenyl(3'-5')phophoadenine
• 英文别名: adenylyl(3'-5')adenosine；ApA；Adenylyl-(3'-5')-adenosine；[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate
• CAS: 2391-46-0
• 化学式: C₂₀H₂₅N₁₀O₁₀P
• 分子量: 596.453
• InChiKey: UYSXBCQACJTYFS-XPWFQUROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  294
• 氢给体数：
  7
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  adenyl(3'-5')phophoadenine 在 cis-{triethylenetetraminecobalt(III)Cl₂}Cl 作用下， 生成 腺苷
  参考文献：
  名称：

  三亚乙基四胺钴（III）有效裂解腺苷基（3'-5'）腺苷

  摘要：

  在[pD 6]，50°C下，[Co（三亚乙基四胺）（H 2 O）2 ] 3+（0.2 M）促进腺苷酸（3'-5'）腺苷的裂解10 5倍。

  DOI：

  10.1039/c39900001050
• 作为产物：
  描述：

  2',3'-异丙叉腺苷 在 吡啶 、 甲酸 、 silver(I) acetate 作用下， 反应 32.25h， 生成 adenyl(3'-5')phophoadenine
  参考文献：
  名称：

  Agrawal, Sudhir; Misra, Krishna, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 2, p. 132 - 134

  摘要：

  DOI：

文献信息

• A Nucleotide Dimer Synthesis Without Protecting Groups Using Montmorillonite as Catalyst
  作者：Prakash C. Joshi、Michael F. Aldersley、Dmitri V. Zagorevskii、James P. Ferris

  DOI：10.1080/15257770.2012.701787

  日期：2012.7

  including heterochiral and chimeric syntheses. This greener chemistry has enabled the synthesis of dimers from activated nucleotides themselves, activated nucleotides with nucleosides, and activated nucleotides with nucleotide 5′-monophosphates. [Supplemental materials are available for this article. Go to the publisher's online edition of Nucleosides, Nucleotides & Nucleic Acids to view the free supplemental

  已经开发了提供包含天然或非天然核苷残基的核苷酸二聚体的合成。在不存在保护基的情况下，将核糖核苷5'-磷酰胺基咪唑化物添加到吸附在蒙脱石上的核苷中性pH下。大约30％的咪唑化物被转化为2'-5'二聚体和3'-5'二聚体，其余的则被水解为5'-单磷酸酯。通过多种组合进行的实验表明，该方法可能会受到限制，包括杂手性和嵌合合成。这种绿色化学方法使得能够从活化的核苷酸本身，具有核苷的活化核苷酸和具有核苷酸5'-单磷酸酯的活化核苷酸合成二聚体。 [本文提供补充材料。转到发布者的在线版《核苷酸，核苷酸和核酸》以查看免费的补充文件。]
• Rapid and highly base selective RNA cleavage by a dinuclear Cu(II) complex
  作者：Shanghao Liu、Andrew D. Hamilton

  DOI：10.1039/a808195f

  日期：——

  A bis-Cu(II) complex based on a covalently linked terpyridine and bipyridine ligand system is shown to rapidly cleave bis-ribonucleotides with remarkable selectivity for adenine bases.

  基于共价连接的吡啶并三吡啶和联吡啶配体系统的二铜(II)配合物，显示出对腺嘌呤基具有显著选择性的双核糖核酸快速切割能力。
• Synthesis and enhanced DNA cleavage activities of bis-tacnorthoamide derivatives
  作者：Li Wei、Ying Shao、Mi Zhou、Hong-Wen Hu、Guo-Yuan Lu

  DOI：10.1039/c2ob25743b

  日期：——

  A new metal-free DNA cleaving reagent, bis-tacnorthoamide derivative 1 with two tacnorthoamide (tacnoa) units linked by a spacer containing anthraquinone, has been synthesized from triazatricyclo[5.2.1.04,10]decane and characterized by NMR and mass spectrometry. For comparison, the corresponding compounds mono-tacnorthoamide derivative 2 with one tacnorthoamide unit and 6 with two tacnorthoamide units linked by an alkyl (1,6-hexamethylene) spacer without anthraquinone have also been synthesized. The DNA-binding property investigated via fluorescence and CD spectroscopy suggests that compounds 1 and 2 have an intercalating DNA binding mode, and the apparent binding constants of 1, 2 and 6 are 1.3 × 107 M−1, 0.8 × 107 M−1 and 8 × 105 M−1, respectively. Agarose gel electrophoresis was used to assess plasmid pUC19 DNA cleavage activity promoted by 1, 2, 6 and parent tacnoa under physiological conditions, which gives rate constants kobs of 0.2126 ± 0.0055 h−1, 0.0620 ± 0.0024 h−1, 0.040 ± 0.0007 h−1 and 0.0043 ± 0.0002 h−1, respectively. The 50-fold and 15-fold rate acceleration over parent tacnoa is because of the anthraquinone moiety of compound 1 or 2 intercalating into DNA base pairs via a stacking interaction. Moreover, DNA cleavage reactions promoted by compound 1 give 5.3-fold rate acceleration over compound 6, which further demonstrates that the introduction of anthraquinone results in a large enhancement of DNA cleavage activity. In particular, DNA cleavage activity promoted by 1 bearing two tacnoa units is 3.3 times more effective than 2 bearing one tacnoa unit and the DNA cleavage by compound 1 was achieved effectively at a relatively low concentration (0.03 mM). This dramatic rate acceleration suggests the cooperative catalysis of the two positively charged tacnoa units in compound 1. The radical scavenger inhibition study and ESI-MS analysis of bis(2,4-dinitrophenyl) phosphate (BDNPP) and adenylyl(3′-5′)phosphoadenine (APA) cleavage in the presence of compound 1 suggest the cleavage mechanism would be via a hydrolysis pathway by cleaving the phosphodiester bond of DNA.

  一种新型无金属DNA切割试剂，即由包含蒽醌的间隔基连接的两个tacnoa（tacnorthoamide）单元的双tacnoa衍生物1，已从三氮杂三环[5.2.1.04,10]癸烷合成并由NMR和质谱进行表征。为了比较，还合成了相应的单tacnoa衍生物2（含有一个tacnoa单元）和6（含有两个tacnoa单元，通过不含蒽醌的烷基（1,6-己二基）间隔基连接）。通过荧光和圆二色光谱调查的DNA结合性质表明，化合物1和2具有插入式DNA结合模式，其表观结合常数分别为1.3 × 10^7 M^-1、0.8 × 10^7 M^-1和8 × 10^5 M^-1。使用琼脂糖凝胶电泳评估在生理条件下由1、2、6和母体tacnoa促进的质粒pUC19 DNA切割活性，分别得到速率常数kobs为0.2126 ± 0.0055 h^-1、0.0620 ± 0.0024 h^-1、0.040 ± 0.0007 h^-1和0.0043 ± 0.0002 h^-1。相比于母体tacnoa，速率分别提高了50倍和15倍，这是由于化合物1或2的蒽醌部分通过堆叠相互作用插入到DNA碱基对中。此外，由化合物1促进的DNA切割反应的速率比化合物6提高了5.3倍，进一步证明蒽醌的引入大大增强了DNA切割活性。特别是，具有两个tacnoa单元的1促进的DNA切割活性比具有一个tacnoa单元的2高出3.3倍，并且在相对较低的浓度（0.03 mM）下有效实现了化合物1的DNA切割。这种显著的速率加速表明化合物1中的两个正电荷tacnoa单元之间的协同催化作用。自由基清除剂抑制研究和ESI-MS分析显示，在化合物1存在下，双（2,4-二硝基苯基）磷酸（BDNPP）和腺苷(3′-5′)磷酸腺苷（APA）的切割表明切割机制是通过水解途径切割DNA的磷酸二酯键。
• Lanthanide Complexes with High Stability and Efficiency for the Hydrolysis of a Ribonucleotide Dimer
  作者：Morio Yashiro、Akira Ishikubo、Tohru Takarada、Makoto Komiyama

  DOI：10.1246/cl.1995.665

  日期：1995.8

  Lanthanide complexes with N,N,N′,N′-tetrakis[(2-pyridyl)methyl]ethylenediamine (TPEN) efficiently hydrolyze a ribonucleotide dimer, ApA, at 35 °C, pH = 7.2. The activity of La3+-TPEN is greater than that of free La3+ ion. The Ln3+-TPEN complexes are sufficiently stable in neutral aqueous solutions (the formation constants are in the range log K/mol−1 dm3 = 3.9 - 6.2). These complexes are promising for the active site of artificial ribonucleases.

  具有N,N,N′,N′-四[(2-吡啶基)甲基]乙二胺（TPEN）的镧系金属配合物能够在35°C，pH = 7.2下高效水解核糖核苷二聚体ApA。La3+-TPEN的活性高于游离La3+离子。Ln3+-TPEN配合物在中性水溶液中具有足够的稳定性（形成常数在log K/mol−1 dm3 = 3.9 - 6.2的范围内）。这些配合物在人工核糖核酸酶的活性位点上显示出良好的前景。
• Dinuclear Zn²⁺complexes in the hydrolysis of the phosphodiester linkage in a diribonucleoside monophosphate diester
  作者：Morio Yashiro、Hideki Kaneiwa、Kenichi Onaka、Makoto Komiyama

  DOI：10.1039/b312301d

  日期：——

  Dizinc complexes that were formed from 2 ∶ 1 mixtures of Zn(NO3)2 and dinucleating ligands TPHP (1), TPmX (2) or TPpX (3) in aqueous solutions efficiently hydrolyzed diribonucleoside monophosphate diesters (NpN) under mild conditions. The dinucleating ligand affected the structure of the aquo-hydroxo-dizinc core, resulting in different characteristics in the catalytic activities towards NpN cleavage. The pH-rate profile of ApA cleavage in the presence of (Zn2+)2-1 was sigmoidal, whereas those of (Zn2+)2-2 and (Zn2+)2-3 were bell-shaped. The pH titration study indicated that (Zn2+)2-1 dissociates only one aquo proton (up to pH 12), whereas (Zn2+)2-2 dissociates three aquo protons (up to pH 10.7). The observed differences in the pH-rate profile are attributable to the various distributions of the monohydroxo-dizinc species, which are responsible for NpN cleavage. As compared to that using (Zn2+)2-1, the NpN cleavage using (Zn2+)2-2 showed a greater rate constant, with a higher product ratio of 3′-NMP/2′-NMP. The saturation behaviors of the rate, with regard to the concentration of NpN, were analyzed by Michaelis–Menten type kinetics. Although the binding of (Zn2+)2-2 to ApA was weaker than that of (Zn2+)2-1, (Zn2+)2-2 showed a greater kcat value than (Zn2+)2-1, resulting in higher ApA cleavage activity of the former.

  由2:1的Zn(NO3)2与双配体TPHP（1）、TPmX（2）或TPpX（3）在水溶液中形成的二锌复合物在温和条件下有效水解二核苷酸单磷酸二酯（NpN）。双配体的结构影响了水合羟基二锌核心的构造，导致其催化NpN裂解的活性特征有所不同。在（Zn2+)2-1存在下，ApA裂解的pH-速率曲线呈S型，而（Zn2+)2-2和（Zn2+)2-3的曲线则呈钟形。pH滴定研究表明，（Zn2+)2-1仅在pH达到12时解离一个水合质子，而（Zn2+)2-2在pH达到10.7时则解离三个水合质子。观察到的pH-速率曲线差异可归因于单羟基二锌物种的不同分布，这些物种是NpN裂解的关键。与使用（Zn2+)2-1相比，使用（Zn2+)2-2时的NpN裂解表现出更大的速率常数，且3′-NMP/2′-NMP的产物比例更高。关于NpN浓度的速率饱和行为通过米氏动力学分析。尽管（Zn2+)2-2对ApA的结合强度弱于（Zn2+)2-1，但（Zn2+)2-2的kcat值高于（Zn2+)2-1，导致前者在ApA裂解中的活性更强。