9-{5-[(3-氨基-3-羧基丙基)(甲基)-lambda4-硫基]-5-脱氧呋喃戊糖基}-9H-嘌呤-6-胺 | 111093-45-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 中文名称: 9-{5-[(3-氨基-3-羧基丙基)(甲基)-lambda4-硫基]-5-脱氧呋喃戊糖基}-9H-嘌呤-6-胺
• 英文名称: ³H-SAM
• 英文别名: S-adenosyl-L-[methyl-3H]methionine；[³H]S-adenosyl-methionine；S-Adenosyl-L-[methyl-3H]methionine；(2S)-2-amino-4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-(tritritiomethyl)sulfonio]butanoate
• CAS: 111093-45-9
• 化学式: C₁₅H₂₂N₆O₅S
• 分子量: 404.419
• InChiKey: MEFKEPWMEQBLKI-QGRBLFOHSA-N

物化性质

• 闪点：
  58 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  187
• 氢给体数：
  4
• 氢受体数：
  10

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• 危险品运输编号：
  UN 2910 7

反应信息

• 作为反应物：
  描述：

  可可碱 、 9-{5-[(3-氨基-3-羧基丙基)(甲基)-lambda4-硫基]-5-脱氧呋喃戊糖基}-9H-嘌呤-6-胺 在 Paullinia cupana caffeine synthase 作用下， 以 aq. buffer 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit

  摘要：

  Guarana seeds have the highest caffeine concentration among plants accumulating purine alkaloids, but in contrast with coffee and tea, practically nothing is known about caffeine metabolism in this Amazonian plant. In this study, the levels of purine alkaloids in tissues of five guarana cultivars were determined. Theobromine was the main alkaloid that accumulated in leaves, stems, inflorescences and pericarps of fruit, while caffeine accumulated in the seeds and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid concentration, whether theobromine or caffeine, was higher in young/immature tissues, then decreasing with plant development/maturation. Caffeine synthase activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was assembled with sequences retrieved from the EST database REALGENE using sequences of caffeine synthase from coffee and tea, whose expression was also highest in seeds from immature fruit. The PcCS has 1083bp and the protein sequence has greater similarity and identity with the caffeine synthase from cocoa (BTS1) and tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7-trimethylxanthine), respectively. Among several substrates tested, PcCS showed higher affinity for theobromine, differing from all other caffeine synthases described so far, which have higher affinity for paraxanthine. When compared to previous knowledge on the protein structure of coffee caffeine synthase, the unique substrate affinity of PcCS is probably explained by the amino acid residues found in the active site of the predicted protein.

  DOI：

  10.1016/j.phytochem.2014.04.018
• 作为产物：
  描述：

  5'-氯-5'-脱氧腺苷 、 L-蛋氨酸[甲基-3H] 在 bacterial chlorinase (SalL) 作用下， 以 aq. phosphate buffer 为溶剂， 反应 2.5h， 生成 9-{5-[(3-氨基-3-羧基丙基)(甲基)-lambda4-硫基]-5-脱氧呋喃戊糖基}-9H-嘌呤-6-胺
  参考文献：
  名称：

  人 DNA 甲基转移酶 1 过渡态类似物抑制剂的合成和表征

  摘要：

  人类 DNA 甲基转移酶 1 (DNMT1) 对 CpG 区域的高甲基化使肿瘤抑制基因沉默，而对 DNMT1 的抑制可以重新激活沉默的基因。5-氮杂胞苷是经批准的 DNMT1 抑制剂，但它们的诱变机制限制了它们的效用。来自S-腺苷高半胱氨酸、蛋氨酸和脱氧胞苷类似物的合成子方法在 16 种化学稳定的过渡态模拟物的合成中概括了 DNMT1 过渡态的化学特征。对引起纯化的DNMT1的完全和部分抑制的抑制剂进行了表征。抑制剂对 DNMT1 与 DNMT3b 显示出适度的选择性。活性位点对接预测抑制剂与S-腺苷-l的相互作用催化位点的甲硫氨酸和脱氧胞苷区域，通过直接结合分析进行验证。纯化的 DNMT1 的抑制剂作用未反映在培养的细胞中。部分抑制剂激活细胞 DNA 甲基化，而完全抑制剂对细胞 DNA 甲基化没有影响。这些化合物提供了对用于 DNA 甲基转移酶的新的非共价 DNMT 化学支架家族的化学访问。

  DOI：

  10.1021/acs.jmedchem.1c01869

文献信息

• Effect of substrate features and mutagenesis of active site tyrosine residues on the reaction course catalysed by <i>Trypanosoma brucei</i> sterol C-24-methyltransferase
  作者：Jialin Liu、Kulothungan Ganapathy、Ewa Wywial、Janusz M. Bujnicki、Chizaram A. Nwogwugwu、W. David Nes

  DOI：10.1042/bj20110865

  日期：2011.11.1

  product set consisting of Δ24(25)-, Δ24(28)- and Δ25(27)-olefins. The C-methylation reaction requires Si(β)-face C-24-methyl addition coupled to reversible migration of positive charge from C-24 to C-25. The hydride shifts responsible for charge migration in formation of multiple ergostane olefin isomers catalysed by TbSMT were examined by incubation of a series of sterol acceptors paired with AdoMet (S

  TbSMT [布鲁氏锥虫24-SMT（甾醇C-24-甲基转移酶）]合成了由Δ24（25）-，Δ24（28）-和Δ25（27）-烯烃组成的非常规24烷基固醇产物集。C-甲基化反应需要Si（β）-面C-24-甲基加成，再加上正电荷从C-24到C-25的可逆迁移。通过与AdoMet（S-腺苷-L-蛋氨酸）配对的一系列固醇受体的孵育，研究了由TbSMT催化形成多种麦角锡烷烯烃异构体中电荷迁移的氢化物转移。用zymosterol与相应的24-2H和27-13C衍生物进行比较所得到的结果表明，在氢化物转移反应中，在形成24-甲基-Δ24（25）-烯烃产物的路径上，同位素敏感分支（动力学同位素效应，kH / kD = 1.20），在C28分支和C27顺式末端甲基处的立体特异性CH3→CH2消除分别形成Δ24（28）和Δ25（27）产物。Cholesta-5,7,22,24-tetraenol转化为ergosta-5
• Biochemistry and Molecular Genetics of the Biosynthesis of the Earthy Odorant Methylisoborneol in <i>Streptomyces coelicolor</i>
  作者：Chieh-Mei Wang、David E. Cane

  DOI：10.1021/ja803639g

  日期：2008.7.1

  Methylisoborneol (2) is a volatile organic compound produced by a wide variety of Actinomycetes soil orgainisms, myxobacteria, and cyanobacteria. It has an unusually low odor threshold and, together with geosmin, is responsible for the characteristics smell of moist soil as well as unpleasant taste and odor episodes assoiciated with public water supplies and contamination of various foodstuffs, including fish, wine and beer. Despite considerable interest in detection and remediation of methylisoborneal, the biosynthesis of this methylated monoterpene has been obscure. In Streptomyces coelicor, the sco7700 and sco7701 genes are shown to correspond to a two-gene operon responsible for methylisoborneol biosynthesis. Both genes have been amplified by PCR and the resulting DNA has been cloned and expressed in Escherichia coli. Incubation of recombinant SCO7701 protein, annotated as a possible C-methyltransferase, with geranyl diphosphate (1) and S-adenosylmethionine gave the previously unknown compound. (E)-2-methylgeranyl diphosphate (3). Incubation of 3 in the presence of Mg2+ with recombinant SCO7700, previously annotated only as a possible metal-binding protein or terpenoid synthase, resulted in the formation of 2-methylisoborneal (2). The steady-state kinetic parameters for both biochemical reactions have been determined. Incubation of geranyl diphosphate and S-adenosylmethionine with a mixture of both SCO7700 and SCO7701 resulted in formation of methylisoborneal (2). Cyclization of 2-methylgeranyl diphosphate (3) to methylisoborneal (2) likely involves the intermediacy of 2-methylinalyl diphosphate.
• Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit
  作者：Flávia Camila Schimpl、Eduardo Kiyota、Juliana Lischka Sampaio Mayer、José Francisco de Carvalho Gonçalves、José Ferreira da Silva、Paulo Mazzafera

  DOI：10.1016/j.phytochem.2014.04.018

  日期：2014.9

  Guarana seeds have the highest caffeine concentration among plants accumulating purine alkaloids, but in contrast with coffee and tea, practically nothing is known about caffeine metabolism in this Amazonian plant. In this study, the levels of purine alkaloids in tissues of five guarana cultivars were determined. Theobromine was the main alkaloid that accumulated in leaves, stems, inflorescences and pericarps of fruit, while caffeine accumulated in the seeds and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid concentration, whether theobromine or caffeine, was higher in young/immature tissues, then decreasing with plant development/maturation. Caffeine synthase activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was assembled with sequences retrieved from the EST database REALGENE using sequences of caffeine synthase from coffee and tea, whose expression was also highest in seeds from immature fruit. The PcCS has 1083bp and the protein sequence has greater similarity and identity with the caffeine synthase from cocoa (BTS1) and tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7-trimethylxanthine), respectively. Among several substrates tested, PcCS showed higher affinity for theobromine, differing from all other caffeine synthases described so far, which have higher affinity for paraxanthine. When compared to previous knowledge on the protein structure of coffee caffeine synthase, the unique substrate affinity of PcCS is probably explained by the amino acid residues found in the active site of the predicted protein.
• Synthesis and Characterization of Transition-State Analogue Inhibitors against Human DNA Methyltransferase 1
  作者：Farah Lamiable-Oulaidi、Rajesh K. Harijan、Karl J. Shaffer、Douglas R. Crump、Yan Sun、Quan Du、Shivali A. Gulab、Ashna A. Khan、Andreas Luxenburger、Anthony D. Woolhouse、Simone Sidoli、Peter C. Tyler、Vern L. Schramm

  DOI：10.1021/acs.jmedchem.1c01869

  日期：2022.4.14

  methyltransferase 1 (DNMT1) silences tumor-suppression genes, and inhibition of DNMT1 can reactivate silenced genes. The 5-azacytidines are approved inhibitors of DNMT1, but their mutagenic mechanism limits their utility. A synthon approach from the analogues of S-adenosylhomocysteine, methionine, and deoxycytidine recapitulated the chemical features of the DNMT1 transition state in the synthesis of 16 chemically

  人类 DNA 甲基转移酶 1 (DNMT1) 对 CpG 区域的高甲基化使肿瘤抑制基因沉默，而对 DNMT1 的抑制可以重新激活沉默的基因。5-氮杂胞苷是经批准的 DNMT1 抑制剂，但它们的诱变机制限制了它们的效用。来自S-腺苷高半胱氨酸、蛋氨酸和脱氧胞苷类似物的合成子方法在 16 种化学稳定的过渡态模拟物的合成中概括了 DNMT1 过渡态的化学特征。对引起纯化的DNMT1的完全和部分抑制的抑制剂进行了表征。抑制剂对 DNMT1 与 DNMT3b 显示出适度的选择性。活性位点对接预测抑制剂与S-腺苷-l的相互作用催化位点的甲硫氨酸和脱氧胞苷区域，通过直接结合分析进行验证。纯化的 DNMT1 的抑制剂作用未反映在培养的细胞中。部分抑制剂激活细胞 DNA 甲基化，而完全抑制剂对细胞 DNA 甲基化没有影响。这些化合物提供了对用于 DNA 甲基转移酶的新的非共价 DNMT 化学支架家族的化学访问。