S-adenosylmethionine p-toluenesulfonate

• 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
• 英文名称: S-adenosylmethionine p-toluenesulfonate
• 英文别名: (2S)-2-amino-4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-methylsulfonio]butanoate;4-methylbenzenesulfonic acid
• 化学式: C₇H₇O₃S*C₁₅H₂₃N₆O₅S
• mdl: MFCD00063498
• 分子量: 570.648
• InChiKey: VHPOFDUCFKOUHV-XKGORWRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.32
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  249
• 氢给体数：
  5
• 氢受体数：
  13

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概要：SAM-e（S-腺苷甲硫氨酸）是一种天然存在的甲基自由基供体，参与人类和动物体内的酶促转甲基反应。SAM-e 没有特定的与哺乳相关的用途，但已被用于治疗产后抑郁症、胆汁淤积性黄疸、骨关节炎以及许多其他疾病。SAM-e 口服生物利用度较差。成年人大体上可以很好地耐受 SAM-e。最常见的不良反应是胃肠道反应，如恶心。也有报道出现皮疹。目前没有关于哺乳期间使用 SAM-e 的临床信息。然而，哺乳母亲使用 SAM-e 不太可能对哺乳的婴儿造成任何不良影响，尤其是如果婴儿已经超过2个月大。 膳食补充剂不需要美国食品药品监督管理局的广泛市场前批准。制造商负责确保安全性，但在市场销售前不需要证明膳食补充剂的安全性和有效性。膳食补充剂可能含有多种成分，标签上标注的成分或其含量与实际成分或含量之间常常存在差异。制造商可以与独立组织签订合同，以验证产品或其成分的质量，但这并不证明产品的安全性或有效性。由于上述问题，一个产品的临床测试结果可能不适用于其他产品。关于膳食补充剂的更详细信息可以在 LactMed 网站的其他地方找到。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对哺乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:SAM-e (S-adenosylmethionine) is a naturally occurring methyl radical donor involved in enzymatic transmethylation reactions in humans and animals. SAM-e has no specific lactation-related uses, but it has been used therapeutically for treating postpartum depression, cholestatic jaundice, osteoarthritis and numerous other conditions. SAM-e has poor oral bioavailability. SAM-e is generally well tolerated in adults. The most frequent adverse effects reported are gastrointestinal, such as nausea. Skin rashes have also been reported. No information is available on the clinical use of SAM-e during breastfeeding. However, use of SAM-e by a nursing mother would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Dietary supplements do not require extensive pre-marketing approval from the U.S. Food and Drug Administration. Manufacturers are responsible to ensure the safety, but do not need to prove the safety and effectiveness of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and differences are often found between labeled and actual ingredients or their amounts. A manufacturer may contract with an independent organization to verify the quality of a product or its ingredients, but that does not certify the safety or effectiveness of a product. Because of the above issues, clinical testing results on one product may not be applicable to other products. More detailed information about dietary supplements is available elsewhere on the LactMed Web site. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  (S)-去甲乌药碱 、 S-adenosylmethionine p-toluenesulfonate 在 Coptis japonica cell lysate containing norcoclaurine 6-O-methyltransferase 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 反应 1.5h， 生成 衡州乌药碱; 乌药碱
  参考文献：
  名称：

  结合甲基转移酶的多酶一锅级联用于四氢异喹啉生物碱的战略多样化

  摘要：

  四氢异喹啉 (THIQ) 环系统存在于多种结构多样的天然产物中，表现出广泛的生物活性。通过在体外建立级联反应来模拟此类生物碱的生物合成途径，是一种成功的策略，并且可以提供比传统合成方法更好的立体选择性。 S-腺苷甲硫氨酸 (SAM) 依赖性甲基转移酶对于 THIQ 的生物合成和多样化至关重要；然而，由于 SAM 成本高和底物范围小，它们的体外应用往往受到限制。在这项研究中，我们描述了甲基转移酶在体外多酶级联中的应用，包括原位生成 SAM。在酶制备规模上，使用多达七种酶对天然和非天然 THIQ 进行区域选择性多样化。甲基转移酶的区域选择性取决于 C-1 处的基团和 THIQ 中氟的存在。所使用的儿茶酚甲基转移酶还发现了有趣的双重活性，该酶能够区域选择性地甲基化单个分子中的两种不同的儿茶酚。

  DOI：

  10.1002/anie.202104476

文献信息

• Chemistry of a Unique Polyketide-like Synthase
  作者：Stephanie W. Chun、Meagan E. Hinze、Meredith A. Skiba、Alison R. H. Narayan

  DOI：10.1021/jacs.7b13297

  日期：2018.2.21

  established that this single polypeptide carries out the formation of two carbon-carbon bonds, two decarboxylation events and a stereospecific protonation to afford the linear biosynthetic precursor to STX (4). The synthetic utility of the SxtA AONS is demonstrated by the synthesis of a suite of α-amino ketones from the corresponding α-amino acid in a single step.

  与许多复杂的天然产物一样，石房蛤毒素 (STX) 的复杂结构阻碍了对该支架作为研究电压门控钠离子通道的工具和作为药剂的效用的全面探索。既定的化学策略可以提供获取天然产品的途径；然而，尚未设计出一种能够加快获取相关化合物的石房蛤毒素的化学酶促途径。实现对此类分子的化学酶促方法的第一步是阐明石房蛤毒素生物合成途径。迄今为止，尚未证明 STX 与其假定的生物合成酶之间存在生化联系。在此，我们报告了 STX 生物合成中涉及的任何酶的首次生化表征。具体来说，聚酮化合物样合成酶 SxtA 的化学功能，阐明了来自蓝藻 Cylindrospermopsis raciborskii T3。这种独特的巨量合酶由四个结构域组成：甲基转移酶 (MT)、GCN5 相关的 N-乙酰转移酶 (GNAT)、酰基载体蛋白 (ACP) 以及与多域合成酶。我们已经确定，该单一多肽形成两个碳-碳键、两个脱羧事件和立体有择质子化，以提供
• Chemo-Enzymatic Detection of Protein Isoaspartate Using Protein Isoaspartate Methyltransferase and Hydrazine Trapping
  作者：Joshua F. Alfaro、Laura A. Gillies、He G. Sun、Shujia Dai、Tianzhu Zang、Joshua J. Klaene、Byung Ju Kim、Jonathan D. Lowenson、Steven G. Clarke、Barry L. Karger、Zhaohui Sunny Zhou

  DOI：10.1021/ac800251q

  日期：2008.5.1

  Isoaspartate formation is a ubiquitous post-translation modification arising from spontaneous asparagine deamidation or aspartate isomerization. The formation of isoaspartate inserts a methylene group into the protein backbone, generating a “kink”, and may drastically alter protein structure and function, thereby playing critical roles in a myriad of biological processes, human diseases, and protein pharmaceutical development. Herein, we report a chemo-enzymatic detection method for the isoaspartate protein, which in particular allows the affinity enrichment of isoaspartate-containing proteins. In the initial step, protein isoaspartate methyltransferase selectively converts isoaspartates into the corresponding methyl esters. Subsequently, the labile methyl ester is trapped by strong nucleophiles in aqueous solutions, such as hydrazines to form hydrazides. The stable hydrazide products can be analyzed by standard proteomic techniques, such as matrix-assisted laser desorption ionization and electrospray ionization mass spectrometry. Furthermore, the chemical trapping step allows us to introduce several tagging strategies for product identification and quantification, such as UV−vis and fluorescence detection through a dansyl derivative. Most significantly, the hydrazide product can be enriched by affinity chromatography using aldehyde resins, thus drastically reducing sample complexity. Our method hence represents the first technique for the affinity enrichment of isoaspartyl proteins and should be amendable to the systematic and comprehensive characterization of isoaspartate, particularly in complex systems.

  异天冬氨酸的形成是一种普遍的翻译后修饰，源于天冬氨酸的自发去酰胺化或天冬氨酸的异构化。异天冬氨酸的形成在蛋白质主链中插入一个亚甲基基团，产生一个“扭曲”，并可能显著改变蛋白质的结构和功能，从而在众多生物过程、人类疾病以及蛋白质药物开发中发挥关键作用。在此，我们报道了一种用于检测异天冬氨酸蛋白的化学-酶法检测方法，特别是允许富集含有异天冬氨酸的蛋白质。在初始步骤中，蛋白质异天冬氨酸甲基转移酶选择性地将异天冬氨酸转化为相应的甲酯。随后，易裂解的甲酯在水相溶液中被强亲核试剂捕获，例如肼，形成肼化物。稳定的肼化物产物可以通过标准的蛋白组学技术进行分析，如基质辅助激光解吸电离和电喷雾电离质谱。此外，化学捕获步骤使我们能够引入几种标记策略用于产物识别和定量，例如通过丹磺酰衍生物进行UV-Vis和荧光检测。最重要的是，肼化物产物可以通过使用醛树脂的亲和色谱进行富集，从而显著降低样品复杂性。因此，我们的方法代表了首个异天冬氨酸蛋白亲和富集技术，应能适用于对异天冬氨酸的系统性和全面特征分析，特别是在复杂体系中。
• Towards lipophilic derivatives of S-adenosyl-L-methionine
  作者：Olga Juanes、Pilar Goya、Ana Martinez

  DOI：10.1002/jhet.5570350338

  日期：1998.5

  Two different strategies for the synthesis of S-Adenosyl-L-methionine liphophilic derivatives have been attempted. The first chemical direct modification performed on S-adenosyl-L-methionine is described.

  已经尝试了两种不同的合成S-腺苷-L-蛋氨酸亲脂性衍生物的策略。描述了对S-腺苷-L-蛋氨酸进行的第一化学直接修饰。
• Halomethane Biosynthesis: Structure of a SAM-Dependent Halide Methyltransferase from Arabidopsis thaliana
  作者：Jason W. Schmidberger、Agata B. James、Robert Edwards、James H. Naismith、David O'Hagan

  DOI：10.1002/anie.201000119

  日期：2010.5.10

  It's a gas! The structure of the halomethane‐producing halo/thiocyanate methyltransferase enzyme from plants has been determined. The halide ion and the methyl group of S‐adenosyl‐L‐methionine (SAM) were modeled into the active site (see picture; chloride: green sphere; SAM: C green, O red, S yellow, N blue), which indicated their predisposition for reaction.

  这是一种气体！植物中产生卤代甲烷的卤代/硫氰酸甲基转移酶的结构已被确定。将卤离子和S-腺苷-L-甲硫氨酸 (SAM) 的甲基建模为活性位点（见图；氯化物：绿色球体；SAM：C 绿色、O 红色、S 黄色、N 蓝色），这表明他们的反应倾向。
• Enzymatic <i>O</i>-Methylation of Flavanols Changes Lag Time, Propagation Rate, and Total Oxidation during in Vitro Model Triacylglycerol-Rich Lipoprotein Oxidation
  作者：Jun Yu、Gabe Smith、Heidrun B. Gross、Robert J. Hansen、John Levenberg、Rosemary L. Walzem

  DOI：10.1021/jf060690b

  日期：2006.11.1

  3'-O-Methyl derivatives of flavan-3-ols, (+)-catechin (C), (-)-epicatechin (EC), and (-)-catechin gallate (CG) were prepared enzymatically. Hexanal (EC and CG family, 5 mmol/L) and conjugated diene (C and EC family, 0.25-10 mmol/L) formation following CuSO4-mediated triacylglycerol-rich lipoprotein oxidation was measured. All EC and CG compounds significantly reduced hexanal formation (p < 0.02). O-Methylation

  酶法制备黄烷-3-醇，（+）-儿茶素（C），（-）-表儿茶素（EC）和（-）-儿茶素没食子酸酯（CG）的3'-O-甲基衍生物。测量了在CuSO4介导的富含三酰基甘油的脂蛋白氧化后形成的己醛（EC和CG家族，5 mmol / L）和共轭二烯（C和EC家族，0.25-10 mmol / L）。所有的EC和CG化合物均显着降低了己醛的形成（p <0.02）。O-甲基化提高了CG（极性更大）的能力，同时降低了EC（极性较小）限制己醛形成的能力。3'-O-甲基EC抑制EC形成的能力比EC低18％（p <0.001）和4'-O-甲基65％（p <0.001）。> 1 micromol / L时，所有EC和C化合物的滞后时间均显着增加。母体化合物比代谢物（增加1.5倍）更有效（增加4倍以上）。母体化合物不影响繁殖速率（DeltaOD / min）。在> 1 mmol / L时，O-甲基化的EC和C将传播减少20-40％（p