2-(Methoxyoxalyl-amino)-3-phenyl-propionic acid methyl ester | 141635-23-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(Methoxyoxalyl-amino)-3-phenyl-propionic acid methyl ester
• 英文别名: Methyl 2-[(2-methoxy-2-oxoacetyl)amino]-3-phenylpropanoate
• CAS: 141635-23-6
• 化学式: C₁₃H₁₅NO₅
• 分子量: 265.266
• InChiKey: CAUUPQLNYYFMOQ-UHFFFAOYSA-N

物化性质

• 密度：
  1.216±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(Methoxyoxalyl-amino)-3-phenyl-propionic acid methyl ester 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 2-(Carboxyformamido)-3-phenylpropanoic acid
  参考文献：
  名称：

  Complementary Steric Engineering at the Protein–Ligand Interface for Analogue-Sensitive TET Oxygenases

  摘要：

  Ten-eleven translocation (TET) enzymes employ O-2 earth-abundant iron, and 2-ketoglutarate (2KG) to perform iterative C-H oxidation of 5-methylcytosine in DNA to control expression of the mammalian genome. Given that more than 60 such C-H oxygenases are present in humans, determining context-dependent functions of each of these enzymes is a pivotal challenge. In an effort to tackle the problem, we developed analogue-sensitive TET enzymes to perturb the activity of a specific member. We rationally engineered the TET2-2KG interface to develop TET2 variants with an expanded active site that can be specifically inhibited by the N-oxalylglycine (NOG) derivatives carrying a complementary steric "bump". Herein, we describe the identification and engineering of a bulky gatekeeper residue for TET proteins, characterize the orthogonal mutant-inhibitor pairs, and show generality of the approach. Employing cell-permeable NOG analogues, we show that the TET2 mutant can be specifically inhibited to conditionally modulate cytosine methylation in chromosomal DNA in intact human cells. Finally, we demonstrate application of the orthogonal mutant-inhibitor pair to probe transcriptional activity of a specific TET member in cells. Our work provides a general platform for developing analogue-sensitive 2KG-dependent oxygenases to unravel their functions in diverse signaling processes.

  DOI：

  10.1021/jacs.8b05283
• 作为产物：
  描述：

  甲基戊酰氯 、 DL-苯基丙氨酸甲酯盐酸盐 以 甲苯 为溶剂， 反应 4.0h， 以80%的产率得到2-(Methoxyoxalyl-amino)-3-phenyl-propionic acid methyl ester
  参考文献：
  名称：

  Novel inhibitors of prolyl 4-hydroxylase. 3. Inhibition by the substrate analog N-oxaloglycine and its derivatives

  摘要：

  N-Oxaloglycine (3) is an alpha-ketoglutarate (1) analogue that is a competitive inhibitor of prolyl 4-hydroxylase (EC 1.14.11.2). A study of the structure-activity relationships of some other oxalo derivatives shows that substitution on the glycine moiety modulates activity stereoselectively and that if the omega-carboxylate is homologated or replaced by either acylsulfonamides or anilide, then activity is sharply reduced. This sensitivity to these changes is contrasted with the relative insensitivity of another putative alpha-ketoglutarate analogue, pyridine-2,5-dicarboxylic acid (2), and the implication is discussed that compounds of both series are unlikely to bind to prolyl hydroxylase in the same way even though both inhibit the enzyme competitively.

  DOI：

  10.1021/jm00092a016

文献信息

• METHOD FOR ASSAYING OGFOD1 ACTIVITY
  申请人：Schofield Christopher Joseph

  公开号：US20140051106A1

  公开（公告）日：2014-02-20

  The present invention relates to assays for monitoring activity of OGFOD1 activity, in particular, to assays for identifying modulators of OGFOD1 activity. The invention also relates to assays to monitor the prolyl hydroxylase activity of OGFOD1 on its substrate, the human ribosomal protein RPS23. The invention also enables the introduction of 3-hydroxyprolyl residues into peptides and proteins.

  本发明涉及用于监测OGFOD1活性的检测方法，特别是用于鉴定OGFOD1活性调节剂的检测方法。该发明还涉及用于监测OGFOD1对其底物人类核糖体蛋白RPS23的脯氨酸羟化酶活性的检测方法。该发明还能够将3-羟基脯氨酸残基引入肽和蛋白质中。
• Novel inhibitors of prolyl 4-hydroxylase. 3. Inhibition by the substrate analog N-oxaloglycine and its derivatives
  作者：C. Jane Cunliffe、Trevor J. Franklin、Neil J. Hales、George B. Hill

  DOI：10.1021/jm00092a016

  日期：1992.7

  N-Oxaloglycine (3) is an alpha-ketoglutarate (1) analogue that is a competitive inhibitor of prolyl 4-hydroxylase (EC 1.14.11.2). A study of the structure-activity relationships of some other oxalo derivatives shows that substitution on the glycine moiety modulates activity stereoselectively and that if the omega-carboxylate is homologated or replaced by either acylsulfonamides or anilide, then activity is sharply reduced. This sensitivity to these changes is contrasted with the relative insensitivity of another putative alpha-ketoglutarate analogue, pyridine-2,5-dicarboxylic acid (2), and the implication is discussed that compounds of both series are unlikely to bind to prolyl hydroxylase in the same way even though both inhibit the enzyme competitively.
• MINA53 ASSAYS
  申请人：ISIS INNOVATION LIMITED

  公开号：EP1929035B1

  公开（公告）日：2012-09-19
• A METHOD FOR ASSAYING FTO (2-OXOGLUTARATE DEPENDENT OXYGENASE) ACTIVITY
  申请人：ISIS Innovation Limited

  公开号：EP2171446B1

  公开（公告）日：2013-04-24
• Method for Assaying FTO (2-Oxoglutarate Dependent Oxygenase) Activity
  申请人：Ashcroft Frances Mary

  公开号：US20100216832A1

  公开（公告）日：2010-08-26

  The present invention provides a method for assaying oxygenase activity, the method comprising monitoring oxygenase activity of FTO.