carboxymethyldethio-coenzyme A

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: carboxymethyldethio-coenzyme A
• 英文别名: Carboxymethyldethia coenzyme *a；4-[3-[[(2R)-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]butanoic acid
• 化学式: C₂₃H₃₈N₇O₁₈P₃
• 分子量: 793.512
• InChiKey: SKRDARVCOPFVCP-GRFIIANRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.2
• 重原子数：
  51
• 可旋转键数：
  20
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  384
• 氢给体数：
  10
• 氢受体数：
  22

反应信息

• 作为产物：
  描述：

  phenyl 4'-phosphothiopantothenate 在 pyruvate kinase 、 dephospho-CoA kinase 、 pantothenate kinase 、 deacetyl-[citrate-(pro-3S)-lyase] S-acetyltransferase 磷烯醇丙酮酸 、 pantothenate kinase 、 丹酰尸胺 、 N,N-二甲基甲酰胺 、 5’-三磷酸腺苷 、 magnesium chloride 作用下， 以 various solvent(s) 为溶剂， 反应 26.0h， 生成 carboxymethyldethio-coenzyme A
  参考文献：
  名称：

  One-pot preparation of coenzyme A analogues via an improved chemo-enzymatic synthesis of pre-CoA thioester synthons

  摘要：

  辅酶A类似物通过同时利用三种辅酶A合成酶对泛酸硫酯进行生物转化，并在一步法合成中进行氨基解反应，从而被合成。

  DOI：

  10.1039/b613527g

文献信息

• Synthesis of Novel Analogs of Acetyl Coenzyme A: Mimics of Enzyme Reaction Intermediates
  作者：David P. Martin、Richard T. Bibart、Dale G. Drueckhammer

  DOI：10.1021/ja00090a014

  日期：1994.6

  An improved method for the synthesis of analogs of coenzyme A (CoA) and its thioesters, which are modified in the thiol or thioester moiety, has been developed using a combination of chemical and enzymatic reactions, The enzymes catalyzing the last two steps of CoA biosynthesis were used to prepare a CoA analog (1c) in which an amide bond is replaced by a thioester bond and the thiol group is replaced by a methyl group. Reaction of 1c with a primary amine in aqueous solution results in aminolysis of the thioester linkage to form the desired CoA analog. Reaction with different amines permits the introduction of a variety of functional groups in place of the nor mal thiol or thioester group. This methodology has been used in the synthesis of five new analogs of acetyl-CoA in which the thioester sulfur is replaced by a methylene group and the acetyl group is replaced by carboxylate (14a), nitro (14b), carboxamide (14c), methyl sulfoxide (14d), and methyl sulfone (14e) groups. 14a-c were designed to mimic the possible enolate or enol intermediate in the reaction of citrate synthase and related enzymes. 14a and 14c are potent inhibitors of citrate synthase, with K-i values 1000- and 570-fold lower than the K-m for acetyl-CoA, respectively. CD titrations indicate that 14a and 14c have low affinity for citrate synthase in the absence of oxaloacetate, consistent with their recognition as enol or enolate analogs. 14b is a poor inhibitor of citrate synthase, with affinity slightly lower than that for acetyl-CoA. These results are consistent with generation of the enol form of acetyl-CoA as the nucleophilic intermediate in the reaction of citrate synthase. 14d and 14e were designed to mimic the tetrahedral intermediate or transition state in the reaction of chloramphenicol acetyltransferase and related acetyl-CoA-dependent acetyltransferases. Both compounds are poor inhibitors of chloramphenicol acetyltransferase, with affinities slightly lower than that of acetyl-CoA, indicating that these compounds are not good mimics of the enzyme-bound tetrahedral intermediate or transition state.
• One-pot preparation of coenzyme A analogues via an improved chemo-enzymatic synthesis of pre-CoA thioester synthons
  作者：Marianne van Wyk、Erick Strauss

  DOI：10.1039/b613527g

  日期：——

  Coenzyme A analogues are synthesized in a one-pot preparation by biotransformation of pantothenate thioesters through the simultaneous use of three CoA biosynthetic enzymes, followed by aminolysis.

  辅酶A类似物通过同时利用三种辅酶A合成酶对泛酸硫酯进行生物转化，并在一步法合成中进行氨基解反应，从而被合成。