thioguanosine 5′-triphosphate | 17670-19-8

• 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: thioguanosine 5′-triphosphate
• 英文别名: 6-TGTP；[[(2R,3S,4R,5R)-5-(2-amino-6-sulfanylidene-3H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• CAS: 17670-19-8
• 化学式: C₁₀H₁₆N₅O₁₃P₃S
• 分子量: 539.25
• InChiKey: QENYANNAQSWPLM-UUOKFMHZSA-N

物化性质

• 熔点：
  102 - 104°C
• 沸点：
  1014.2±75.0 °C(Predicted)
• 密度：
  2.68±0.1 g/cm3(Predicted)
• 溶解度：
  甲醇（微溶）、水（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  -5
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  310
• 氢给体数：
  8
• 氢受体数：
  15

安全信息

• 储存条件：
  -20°C，密闭保存，置于干燥处

制备方法与用途

thioguanosine triphosphate triethylamine salt抑制Rac1激活，并阻止白细胞迁移至淋巴细胞中。

反应信息

• 作为反应物：
  描述：

  thioguanosine 5′-triphosphate 在 Thermus virus ribonucleotide reductase P₇₄-23 、 1,4-二巯基-2,3-丁二醇 作用下， 生成 2'-脱氧-6-硫代鸟苷5'-三磷酸酯
  参考文献：
  名称：

  10.1002/cctc.202400181

  摘要：

  AbstractPolyphosphate kinases (PPKs) are valuable biocatalysts for ATP cofactor regeneration as well as for the phosphorylation of non‐canonical nucleotides. The versatility of PPKs in the latter application is defined by their substrate scope. In this study, we investigate the substrate spectrum of the PPK2‐III enzyme from Meiothermus ruber (MrPPK) for the conversion of canonical and non‐canonical (deoxy)‐ribonucleotides. The enzyme shows high substrate promiscuity for purine and to minor degree pyrimidine substrates, with an overall preference for the native substrate AMP. With structure guided rational amino acid exchanges in the active site, we produced an MrPPK variant with improved activity for a broad variety of purine nucleotides. While the preference for AMP is lost, conversion of nucleotides without a 6‐amino function at the purine moiety is increased. This MrPPK variant is a versatile biocatalyst for the synthesis of non‐canonical nucleotides and could also be useful as a GTP cofactor regeneration system.

  DOI：

  10.1002/cctc.202400181
• 作为产物：
  描述：

  Guanosine 5'-triphosphate 在 L-半胱氨酸 、 potassium chloride 、 adenylating enzyme YcfA 、 5’-三磷酸腺苷 、 magnesium chloride 作用下， 生成 thioguanosine 5′-triphosphate
  参考文献：
  名称：

  硫代和硒酰胺的酶促前药样途径

  摘要：

  阐明了一种新的硫代酰胺酶促途径，作为植物病原细菌中抗代谢物 6-硫鸟嘌呤生物合成的一部分。出乎意料的是，腺苷酸化酶形成中间半胱氨酸-S-缀合物，该缀合物被指定的 C−S 裂解酶裂解，这一过程反映了癌症治疗中的前药方法。

  DOI：

  10.1002/anie.202404243

文献信息

• Enzymatic Thioamide Formation in a Bacterial Antimetabolite Pathway
  作者：Agnieszka Litomska、Keishi Ishida、Kyle L. Dunbar、Marco Boettger、Sébastien Coyne、Christian Hertweck

  DOI：10.1002/anie.201804158

  日期：2018.9.3

  6‐Thioguanine (6TG) is a DNA‐targeting therapeutic used in the treatment of various cancers. While 6TG was rationally designed as a proof of concept for antimetabolite therapy, it is also a rare thioamide‐bearing bacterial natural product and critical virulence factor of Erwinia amylovorans, plant pathogens that cause fire blight. Through gene expression, biochemical assays, and mutational analyses

  6-硫鸟嘌呤（6TG）是一种靶向DNA的治疗剂，可用于治疗各种癌症。虽然6TG合理被设计为理念，为抗代谢药治疗的证明，它也是罕见的硫代轴承细菌天然产物和重要致病因子欧文amylovorans，引起火疫病的植物病原体。通过基因表达，生化分析和突变分析，我们确定了一个专门的两方酶体系，该体系由ATP依赖的硫转移酶（YcfA）和硫转移酶（YcfC）组成，该酶负责特殊的氧分选。在6TG的生物合成中发现了硫取代。力学和系统发育研究表明，YcfA介导的6TG生物合成是从支持翻译保真度的古老tRNA修饰演变而来的。6TG硫酰胺化的成功体外重组显示，YcfA使用了专门的硫转运蛋白，与通用RNA相关系统明显不同。这项研究揭示了天然产物生物合成中未充分探索的酶促C-S键形成。
• Catalytic Promiscuity of cGAS: A Facile Enzymatic Synthesis of 2′‐3′‐Linked Cyclic Dinucleotides
  作者：Katrin Rosenthal、Martin Becker、Jascha Rolf、Regine Siedentop、Michael Hillen、Markus Nett、Stephan Lütz

  DOI：10.1002/cbic.202000433

  日期：2020.11.16

  Enzymatic shortcut: Cyclic dinucleotides, which are of great interest to study immunology and immune oncology, can be synthesized in a one‐step biotransformation significantly shortening the chemical synthesis route. The enzyme displays a surprisingly large substrate scope.

  酶促捷径：环状二核苷酸对研究免疫学和免疫肿瘤学非常感兴趣，可以通过一步生物转化来合成，显着缩短化学合成路线。该酶显示出惊人的大底物范围。
• Method for optimizing thiopurine efficacy and toxicity using mass spectrometry
  申请人：Dervieux Thierry

  公开号：US20060216726A1

  公开（公告）日：2006-09-28

  The present invention relates to methods for optimizing therapeutic efficacy or reducing toxicity in a subject receiving a drug providing 6-thioguanine nucleotide. The methods provide determining 6-thioguanine and 6-methyl-mercaptopurine nucleotide concentration levels using an analytical technique having an ionizing source.

  本发明涉及用于优化接受提供6-硫鸟嘌呤核苷的药物的受试者的治疗效果或减少毒性的方法。该方法提供使用具有电离源的分析技术确定6-硫鸟嘌呤和6-甲基巯基嘌呤核苷浓度水平。
• Analogous compounds of 6-thioguanosine triphosphate, their use in medical fields and processes for their preparation
  申请人：Naccari Giancarlo

  公开号：US20090258837A1

  公开（公告）日：2009-10-15

  The invention relates to analogous compounds of 6-thioguanosine triphosphate of general formula (I). A compound of the general formula (I); wherein the dashed bond in the sugar moiety can be either single or double and wherein R1, R2, R3, R4 or R5, equal or different between each other, have general formula -(Int) m -Ter, wherein m is between 0 and 12 and Int and Ter are Internal and Terminal building blocks, wherein Int is selected from the group consisting of formula (II); and Ter is selected from the group consisting of formula (III). And wherein X represents either carbon or nitrogen atom within aromatic ring, Y represents either oxygen or sulphur atom and an additional group Q, group Qi or groups Qi (Qi indicates that the group or several groups may be bound to any unsaturated moiety of the ring) are selected from the group consisting of —OH, —COOH, —N(CH 3 ) 2 , —N(CH 2 —CH 3 ) 2 |—CO—CH 3 , —CO—O—CH 3 , —O—CH 3 , —S—CH 3 , —SO 2 —CH 3 , —CN, —NO 2 or -Halogen elements, and wherein R5 may be formula (IV) and metal and ammonium salts thereof, wherein n is between O and 5, or oxygen or phosphorus is partially or completely replaced by nitrogen, sulphur, methyleno groups or their derivatives. The invention also concerns the uses of the above mentioned compounds in medical field and the process for their preparation.

  本发明涉及6-硫鸟嘌呤三磷酸类似化合物，其通式为(I)。通式(I)的化合物中，糖基中的虚线键可以是单键或双键，其中R1、R2、R3、R4或R5，相互之间相同或不同，具有通式-(Int)m-Ter，其中m在0到12之间，Int和Ter是内部和末端构建块，其中Int从公式(II)所示的群组中选择；Ter从公式(III)所示的群组中选择。其中X代表芳香环内的碳或氮原子，Y代表氧或硫原子，以及附加基团Q、Qi基团或Qi基团（Qi表示该基团或若干基团可以结合到环的任何不饱和基团上）从以下群组中选择：—OH、—COOH、—N（CH3）2、—N（CH2—CH3）2、—CO—CH3、—CO—O—CH3、—O—CH3、—S—CH3、—SO2—CH3、—CN、—NO2或卤素元素，其中R5可以是公式(IV)及其金属和铵盐，其中n在0到5之间，或氧或磷部分或完全被氮、硫、亚甲基基团或其衍生物所取代。本发明还涉及上述化合物在医学领域中的用途以及它们的制备方法。
• Analogous Compounds of 6-Thioguanosine Triphosphate, their use in Medical Fields and Processes for their Preparation
  申请人：Naccari Giancarlo

  公开号：US20120094948A1

  公开（公告）日：2012-04-19

  The invention relates to analogous compounds of 6-thioguanosine triphosphate of general formula (I). A compound of the general formula (I); wherein the dashed bond in the sugar moiety can be either single or double and wherein R1, R2, R3, R4 or R5, equal or different between each other, have general formula -(Int) m -Ter, wherein m is between 0 and 12 and Int and Ter are Internal and Terminal building blocks, wherein Int is selected from the group consisting of formula (II); and Ter is selected from the group consisting of formula (III). And wherein X represents either carbon or nitrogen atom within aromatic ring, Y represents either oxygen or sulphur atom and an additional group Q, group Qi or groups Qi (Qi indicates that the group or several groups may be bound to any unsaturated moiety of the ring) are selected from the group consisting of —OH, —COOH, —N(CH 3 ) 2 , —N(CH 2 —CH 3 ) 2 |—CO—CH 3 , —CO—O—CH 3 , —O—CH 3 , —S—CH 3 , —SO 2 —CH 3 , —CN, —NO 2 or -Halogen elements, and wherein R5 may be formula (IV) and metal and ammonium salts thereof, wherein n is between O and 5, or oxygen or phosphorus is partially or completely replaced by nitrogen, sulphur, methyleno groups or their derivatives. The invention also concerns the uses of the above mentioned compounds in medical field and the process for their preparation.

  本发明涉及6-硫鸟嘌呤三磷酸的类似物化合物，其通式为（I）。通式（I）的化合物；其中糖基中的虚线键可以是单键或双键，其中R1、R2、R3、R4或R5，在彼此之间相等或不同，具有通式-(Int)m-Ter，其中m在0到12之间，Int和Ter是内部和末端构建块，其中Int选择自公式（II）所示的一组；Ter选择自公式（III）所示的一组。其中X表示芳香环中的碳或氮原子，Y表示氧或硫原子，另外的基团Q、基团Qi或基团Qi（Qi表示该基团或几个基团可以与环的任何不饱和基团结合）选择自-OH、-COOH、-N（CH3）2、-N（CH2-CH3）2| -CO-CH3、-CO-O-CH3、-O-CH3、-S-CH3、-SO2-CH3、-CN、-NO2或卤素元素等一组，其中R5可以是公式（IV）及其金属和铵盐，其中n在0到5之间，或氧或磷部分或完全被氮、硫、亚甲基基团或其衍生物所取代。本发明还涉及上述化合物在医学领域中的用途以及它们的制备方法。