Pent-2-en-4-ynyl 4-methylbenzenesulfonate | 677727-51-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Pent-2-en-4-ynyl 4-methylbenzenesulfonate
• 英文别名: pent-2-en-4-ynyl 4-methylbenzenesulfonate
• CAS: 677727-51-4
• 化学式: C₁₂H₁₂O₃S
• 分子量: 236.291
• InChiKey: WLVUXTJOBRUMOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  S-benzyl-L-homocysteine 、 Pent-2-en-4-ynyl 4-methylbenzenesulfonate 在 氨 、 sodium 作用下， 以 乙醇 为溶剂， 以56%的产率得到S-(pent-2-en-4-ynyl)-L-homocysteine
  参考文献：
  名称：

  A sensitive mass spectrum assay to characterize engineered methionine adenosyltransferases with S-alkyl methionine analogues as substrates

  摘要：

  Methionine adenosyltransferases (MATs) catalyze the formation of S-adenosyl-L-methionine (SAM) inside living cells. Recently, S-alkyl analogues of SAM have been documented as cofactor surrogates to label novel targets of methyltransferases. However, these chemically synthesized SAM analogues are not suitable for cell-based studies because of their poor membrane permeability. This issue was recently addressed under a cellular setting through a chemoenzymatic strategy to process membrane-permeable S-alkyl analogues of methionine (SAAMs) into the SAM analogues with engineered MATs. Here we describe a general sensitive activity assay for engineered MATs by converting the reaction products into S-alkylthioadenosines, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) quantification. With this assay, 40 human MAT mutants were evaluated against 7 SAAMs as potential substrates. The structure-activity relationship revealed that, besides better engaged SAAM binding by the MAT mutants (lower Km value in contrast to native MATs), the gained activity toward the bulky SAAMs stems from their ability to maintain the desired linear S(N)2 transition state (reflected by higher K-cat value). Here the 11 17A mutant of human MATI was identified as the most active variant for biochemical production of SAM analogues from diverse SAAMs. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.ab.2013.12.026

文献信息

• A sensitive mass spectrum assay to characterize engineered methionine adenosyltransferases with S-alkyl methionine analogues as substrates
  作者：Rui Wang、Weihong Zheng、Minkui Luo

  DOI：10.1016/j.ab.2013.12.026

  日期：2014.4

  Methionine adenosyltransferases (MATs) catalyze the formation of S-adenosyl-L-methionine (SAM) inside living cells. Recently, S-alkyl analogues of SAM have been documented as cofactor surrogates to label novel targets of methyltransferases. However, these chemically synthesized SAM analogues are not suitable for cell-based studies because of their poor membrane permeability. This issue was recently addressed under a cellular setting through a chemoenzymatic strategy to process membrane-permeable S-alkyl analogues of methionine (SAAMs) into the SAM analogues with engineered MATs. Here we describe a general sensitive activity assay for engineered MATs by converting the reaction products into S-alkylthioadenosines, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) quantification. With this assay, 40 human MAT mutants were evaluated against 7 SAAMs as potential substrates. The structure-activity relationship revealed that, besides better engaged SAAM binding by the MAT mutants (lower Km value in contrast to native MATs), the gained activity toward the bulky SAAMs stems from their ability to maintain the desired linear S(N)2 transition state (reflected by higher K-cat value). Here the 11 17A mutant of human MATI was identified as the most active variant for biochemical production of SAM analogues from diverse SAAMs. (C) 2013 Elsevier Inc. All rights reserved.