6-氯嘌呤核糖甙-5'-O-单磷酸酯钠盐 | 5843-59-4

• 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
• 中文名称: 6-氯嘌呤核糖甙-5'-O-单磷酸酯钠盐
• 英文名称: 6-chloropurine riboside 5'-monophosphate
• 英文别名: 6-Chloropurine ribonucleotide；6-chloro-9-β-D-ribofuranosylpurine 5'-phosphate；6-chloropurine riboside 5'-phosphate；1-(6-chloro-purin-9-yl)-O⁵-phosphono-β-D-1-deoxy-ribofuranose；(1R)-1-(6-chloro-purin-9-yl)-O⁵-phosphono-D-1,4-anhydro-ribitol；(1R)-1-(6-Chlor-purin-9-yl)-O⁵-phosphono-D-1,4-anhydro-ribit；6-Chloroinosine monophosphate；[(2R,3S,4R,5R)-5-(6-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 5843-59-4
• 化学式: C₁₀H₁₂ClN₄O₇P
• 分子量: 366.655
• InChiKey: ALOBOMYIOYNCBS-KQYNXXCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  23
• 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：
  160
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-氯嘌呤核糖甙-5'-O-单磷酸酯钠盐 在 palladium on activated charcoal sodium hydroxide 、 氢气 作用下， 以 甲醇 、 水 、 溶剂黄146 为溶剂， 80.0 ℃ 、206.84 kPa 条件下， 反应 9.0h， 生成 monosodium mono(((2R,3S,4R,5R)-5-(6-((2-aminoethyl)amino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl hydrogen triphosphate)
  参考文献：
  名称：

  Use of adenine nucleotide derivatives to assess the potential of exo-active-site-directed reagents as species- or isozyme-specific enzyme inactivators. 3. Synthesis of adenosine 5'-triphosphate derivatives with N6- or 8-substituents bearing iodoacetyl groups

  摘要：

  Several series of N6- or 8-substituted derivatives of adenosine 5'-triphosphate (ATP) were synthesized. N6-(omega-Aminoalkyl) derivatives of adenosine 5'-monophosphate (AMP) were converted into their omega-N-carbobenzyloxy derivatives, and these were converted, via the 2',3'-O-carbonyl derivatives of their 5'-phosphorimidazolidates, into the corresponding ATP derivatives. Hydrogenolytic removal of the carbobenzyloxy groups, followed by iodoacetylation of the omega-amino groups with N-(iodoacetoxy)succinimide, gave N6-R-ATP, where R = (CH2)nNHCOCH2I (n = 2--8) or (CH2)nCON)CH3)(CH2)mN(CH3)CO(CH2)nNHCOCH2I (n = m = 3; n = 3, m = 4; n = 4, m = 3; n = m = 4). Condensation of N6-(omega-aminoalkyl) derivatives of AMP with N-hydroxysuccinimide esters of omega-[N-(carbobenzyloxy)amino] carboxylic acids gave N6-(CH2)nNHCO(CH2)mNH-Cbz derivatives of AMP which, upon conversion to the corresponding derivatives of ATP, followed by removal of the carbobenzyloxy group and iodoacetylation, as described above, gave N6-(CH2)nNHCO(CH2)mNHCOCH2I-ATP derivatives (n = 3, m = 5 or 6; n = 4, m = 5; n = 6, m = 1--6). The same sequence of reactions starting with N6-[omega-(methylamino)alkyl] derivatives of N6-CH3-AMP gave N6-CH3, N6-(CH2)nH(CH3)CO(CH2)mNHCOCH2I derivatives of ATP (n = 4, m = 3, 5 or 6; n = 6, m = 5 or 6). Reaction of alpha, omega-diaminoalkanes with 8-Br-ATP gave 8-NH(CH2)nNH2 derivatives of ATP, which upon iodoacetylation gave 8-NH(CH2)nNHCOCH2I derivatives of ATP (n = 2, 4, 6, or 8). Substrate and inhibitor properties indicated that the ATP derivatives are potential exco-ATP-site-directed inactivators of hexokinases, adenylate kinases, and pyruvate kinases.

  DOI：

  10.1021/jm00346a009
• 作为产物：
  描述：

  6-氯-9-beta-D-(2,3-异亚丙基)呋喃核糖基嘌呤 生成 6-氯嘌呤核糖甙-5'-O-单磷酸酯钠盐
  参考文献：
  名称：

  Nucleotides. I. Syntheses of 6-Chloro-, 6-Mercapto-, and 2-Amino-6-mercapto-9-β-D-ribofuranosylpurine 5'-Phosphates¹

  摘要：

  DOI：

  10.1021/ja01462a030

文献信息

• REAGENTS AND METHODS FOR SIRTUIN CAPTURE
  申请人：SAUVE Anthony A.

  公开号：US20130065248A1

  公开（公告）日：2013-03-14

  The invention provides a method of preparing a sirtuin complex. The invention also provides a method of detecting a sirtuin in a sample comprising use of the aforesaid sirtuin complex.

  这项发明提供了一种制备sirtuin复合物的方法。该发明还提供了一种检测样品中sirtuin的方法，包括使用上述sirtuin复合物。
• Reagents and methods for sirtuin capture
  申请人：Sauve Anthony A.

  公开号：US09290791B2

  公开（公告）日：2016-03-22

  The invention provides a method of preparing a sirtuin complex, a method for detecting a sirtuin in a sample, and a method of screening for compounds which inhibit the deacetylase activity of a sirtuin. The method includes (a) providing a sirtuin substrate having the formula: (b) providing NAD+ or an NAD+ analog having the formula: and (c) providing a sirtuin, wherein R1-R4, A1, A2, and n are as defined herein.

  这项发明提供了一种制备sirtuin复合物的方法，一种检测样品中sirtuin的方法，以及一种筛选抑制sirtuin去乙酰化酶活性的化合物的方法。该方法包括(a)提供具有以下公式的sirtuin底物： (b)提供具有以下公式的NAD+或NAD+类似物： 以及(c)提供sirtuin，其中R1-R4，A1，A2和n如本文所定义。
• SUBSTITUTION DERIVATIVES OF N6-BENZYLADENOSINE-5' -MONOPHOSPHATE, METHODS OF PREPARATION THEREOF, USE THEREOF AS MEDICAMENTS, AND THERAPEUTIC PREPARATIONS CONTAINING THESE COMPOUNDS
  申请人：Zatloukal Marek

  公开号：US20130040908A1

  公开（公告）日：2013-02-14

  Substitution derivatives of N 6 -benzyladenosine-5′-monophosphate of the general formula I, wherein (R) n represents 1 to 4 substituents (n is in the range 1-4), which can be the same or different, and R is selected from the group comprising C 1 to C 8 alkyl, C 1 to C 8 alkoxy, amino, halogen, hydroxy, mercapto and nitro groups, and the pharmaceutically acceptable salts thereof. A Method for their preparation, their use as medicaments and in other applications, and a therapeutic composition containing these derivatives is also disclosed.

  通式I的N6-苄基腺苷-5'-磷酸的取代衍生物，其中（R）n表示1至4个取代基（n在1-4范围内），可以相同也可以不同，R选自包括C1到C8烷基，C1到C8烷氧基，氨基，卤素，羟基，巯基和硝基基团的群体，并且其药用盐。还公开了它们的制备方法，作为药物和其他应用中的使用，以及含有这些衍生物的治疗组合物。
• Mechanism-based affinity capture of sirtuins
  作者：Yana Cen、Jessica N. Falco、Ping Xu、Dou Yeon Youn、Anthony A. Sauve

  DOI：10.1039/c0ob00774a

  日期：——

  The ability to probe for catalytic activities of enzymes and to detect their abundance in complex biochemical contexts has traditionally relied on a combination of kinetic assays and techniques such as western blots that use expensive reagents such as antibodies. The ability to simultaneously detect activity and isolate a protein catalyst from a mixture is even more difficult and currently impossible in most cases. In this manuscript we describe a chemical approach that achieves this goal for a unique family of enzymes called sirtuins using novel chemical tools, enabling rapid detection of activity and isolation of these protein catalysts. Sirtuin deacetylases are implicated in the regulation of many physiological functions including energy metabolism, DNA-damage response, and cellular stress resistance. We synthesized an aminooxy-derivatized NAD+ and a pan-sirtuin inhibitor that reacts on sirtuin active sites to form a chemically stable complex that can subsequently be crosslinked to an aldehyde-substituted biotin. Subsequent retrieval of the biotinylated sirtuin complexes on streptavidin beads followed by gel electrophoresis enabled simultaneous detection of active sirtuins, isolation and molecular weight determination. We show that these tools are cross reactive against a variety of human sirtuin isoforms including SIRT1, SIRT2, SIRT3, SIRT5, SIRT6 and can react with microbial derived sirtuins as well. Finally, we demonstrate the ability to simultaneously detect multiple sirtuin isoforms in reaction mixtures with this methodology, establishing proof of concept tools for chemical studies of sirtuins in complex biological samples.

  探测酶的催化活性以及在复杂生化环境中检测其丰度的能力，传统上依赖于动力学测定和诸如使用昂贵试剂（如抗体）的西方印迹等技术。能够同时检测活性并从混合物中分离蛋白催化剂更为困难，在大多数情况下几乎不可能。在本手稿中，我们描述了一种化学方法，利用新型化学工具实现这一目标，针对一种独特的酶家族——去乙酰化酶（sirtuins），从而使得能够快速检测其活性并分离这些蛋白催化剂。去乙酰化酶与许多生理功能的调节相关，包括能量代谢、DNA损伤应答和细胞应激抵抗。我们合成了一种氨氧基衍生的NAD+和一种泛去乙酰化酶抑制剂，该抑制剂会在去乙酰化酶的活性位点反应，形成一种化学稳定的复合物，随后可以与醛基取代的生物素交联。通过链霉亲和素珠子回收生物素化的去乙酰化酶复合物，再通过胶体电泳，我们实现了对活性去乙酰化酶的同时检测、分离和分子量测定。我们展示了这些工具能与多种人类去乙酰化酶亚型（包括SIRT1、SIRT2、SIRT3、SIRT5、SIRT6）交叉反应，并且也能与微生物来源的去乙酰化酶反应。最后，我们展示了能够在反应混合物中同时检测多个去乙酰化酶亚型，确立了在复杂生物样品中进行去乙酰化酶化学研究的概念验证工具。
• Five-Component Cascade Synthesis of Nucleotide Analogues in an Engineered Self-Immobilized Enzyme Aggregate
  作者：Robert A. Scism、Brian O. Bachmann

  DOI：10.1002/cbic.200900620

  日期：——

  Pathway in a particle: A five‐enzyme biosynthetic pathway was self‐immobilized to form a single biocatalyst for generation of purine nucleotide analogues from D‐ribose. This method provides an alternative to engineering biosynthetic pathways in whole cells that obviates problems associated with toxicity, transport and genetic regulation.

  颗粒中的途径：五种酶的生物合成途径是自固定的，可形成单一的生物催化剂，用于从D-核糖生成嘌呤核苷酸类似物。该方法提供了一种工程化全细胞生物合成途径的替代方法，从而消除了与毒性，转运和基因调控有关的问题。