4,5-tryptophan-dione | 129784-88-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4,5-tryptophan-dione
• 英文别名: tryptophan-4,5-dione；(2S)-2-amino-3-(4,5-dioxo-1H-indol-3-yl)propanoic acid
• CAS: 129784-88-9
• 化学式: C₁₁H₁₀N₂O₄
• 分子量: 234.211
• InChiKey: NUSQIWNBKCIPCW-LURJTMIESA-N

物化性质

• 沸点：
  552.1±50.0 °C(Predicted)
• 密度：
  1.573±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,5-tryptophan-dione 在 ammonium hydroxide 、 air 、 溶剂黄146 作用下， 生成 6,8-bi-S-glutathionyl-α-amino-2-carboxy-10,11-dihydro-10,11-dioxo-11bH-indolo[2',3':4,5]furo[3,2-h]pyrrolo(4,3,2-de)quinoline-11b-propanoic acid
  参考文献：
  名称：

  7-S-Glutathionyltryptophan-4,5-dione: Formation from 5-Hydroxytryptophan and Reactions with Glutathione

  摘要：

  The electrochemically driven oxidation of 5-hydroxytryptophan (5-HTPP) in the presence of free glutathione (GSH) yields 4-S-glutathionyl-5-hydroxytryptophan (5) and 7S-glutathionyltryptophan-4,5-dione (7). The latter glutathionyl conjugate is formed both by nucleophilic addition of GSH to tryptophan-4,5-dione (4), a normal product of the oxidation of 5-HTPP, and by oxidation of 5 in a reaction where the glutathionyl residue migrates from the C(4)- to the C(7)-position. In the presence of free GSH 7 reacts to give the 3,7- and 6,7-bi-S-glutathionyl conjugates of 4 and, as a result of intramolecular cyclization reactions, a number of glutathionyl conjugates of an unusual tricyclic pyrroloquinoline. It is speculated that one or more of these products might represent aberrant oxidative metabolites that have been detected in the cerebrospinal fluid of patients with Alzheimer's Disease. (C) 1996 Academic Press, Inc.

  DOI：

  10.1006/bioo.1996.0012
• 作为产物：
  描述：

  5-羟基-L-色氨酸 在 盐酸 作用下， 生成 4,5-tryptophan-dione
  参考文献：
  名称：

  7-S-Glutathionyltryptophan-4,5-dione: Formation from 5-Hydroxytryptophan and Reactions with Glutathione

  摘要：

  The electrochemically driven oxidation of 5-hydroxytryptophan (5-HTPP) in the presence of free glutathione (GSH) yields 4-S-glutathionyl-5-hydroxytryptophan (5) and 7S-glutathionyltryptophan-4,5-dione (7). The latter glutathionyl conjugate is formed both by nucleophilic addition of GSH to tryptophan-4,5-dione (4), a normal product of the oxidation of 5-HTPP, and by oxidation of 5 in a reaction where the glutathionyl residue migrates from the C(4)- to the C(7)-position. In the presence of free GSH 7 reacts to give the 3,7- and 6,7-bi-S-glutathionyl conjugates of 4 and, as a result of intramolecular cyclization reactions, a number of glutathionyl conjugates of an unusual tricyclic pyrroloquinoline. It is speculated that one or more of these products might represent aberrant oxidative metabolites that have been detected in the cerebrospinal fluid of patients with Alzheimer's Disease. (C) 1996 Academic Press, Inc.

  DOI：

  10.1006/bioo.1996.0012

文献信息

• Selective incorporation of 5-hydroxytryptophan into proteins in mammalian cells
  申请人：Zhang Zhiwen

  公开号：US20050136513A1

  公开（公告）日：2005-06-23

  This invention provides methods and compositions for incorporation of an unnatural amino acid into a peptide using an orthogonal aminoacyl tRNA synthetase/tRNA pair. In particular, an orthogonal pair is provided to incorporate 5-hydroxy-L-tryptophan in a position encoded by an opal mutation.

  本发明提供了使用正交氨基酰 tRNA 合成酶/tRNA 对将非天然氨基酸掺入肽中的方法和组合。特别是提供了一种正交对，用于将 5-羟基-L-色氨酸掺入蛋白石突变编码的位置。
• Oxidation Chemistry of 5-[[3-(2-Amino-2-carboxyethyl)-5-hydroxy-1H-indol-4-yl]oxy]-[3-(2-amino-2-carboxyethyl)]-1H-indole: A Putative Aberrant Metabolite of 5-Hydroxytryptophan
  作者：Z. Wu、X.M. Shen、G. Dryhurst

  DOI：10.1006/bioo.1995.1018

  日期：1995.9

  Oxidative damage is known to occur in certain regions of the brain in a number of neurodegenerative disorders that include Alzheimer's Disease (AD) and transient cerebral ischemia and as a result of methamphetamine abuse. Furthermore, aberrant but unknown oxidized forms of 5-hydroxytryptophan (5-HTPP) and 5-hydroxytryptamine (5-HT) have been detected in the cerebrospinal fluid (CSF) of AD patients but not in that of age-matched controls. Accordingly, it is possible that aberrant oxidative metabolites of 5-HTPP and 5-HT might play roles in the neurodegenerative processes that occur in the AD brain and other neurodegenerative disorders. Previous studies have established that the title compound (1) is among the products of the electrochemically driven and various enzyme-mediated oxidations of 5-HTPP. This investigation has focused on both the electrochemical and peroxidase-mediated oxidations of 1 at physiological pH and has established that this dimer is significantly more easily oxidized than 5-HTPP from which it is derived. Under weakly oxidizing conditions 1 is oxidized via a putative carbocation intermediate to an equimolar mixture of 5-HTPP and tryptophan-4,5-dione (2). Under more strongly oxidizing conditions further oxidation of 5-HTPP gives a C(4)-centered carbocation intermediate that can react with the free hydroxyl residue of 1 to form a trimer, tetramer, and larger oligomers that are subsequently further oxidized ultimately to dione 2. When administered into the brains of mice, 1 is a remarkably lethal compound (LD(50) = 3.3 mu g) and evokes a hyperactivity syndrome. Analyses of the brains of mice during this behavioral response reveal that an acute dose of 1 evokes a significant decrease of norepinephrine (NE) levels. Only minor alterations in whole brain levels of DA and 5-HT occur but levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindole-3-acetic acid are significantly elevated. These results suggest that the hyperactivity syndrome evoked by 1 is related to the elevated release and turnover of NE, DA, and 5-HT. Based upon the results obtained and by comparison with other pharmacologic manipulations that evoke a similar hyperactivity syndrome in mice and rats it appears that 1 might be metabolized in vivo to metabolites that interact with certain 5-HT and perhaps other receptor subpopulations. (C) 1995 Academic Press, Inc.
• SELECTIVE INCORPORATION OF 5-HYROXYTRYPOPHAN INTO PROTEINS IN MAMMALIAN CELLS
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：EP1725251A2

  公开（公告）日：2006-11-29
• EP1725251A4
  申请人：——

  公开号：EP1725251A4

  公开（公告）日：2009-07-01
• Selective Incorporation of 5-hydroxytryptophan into Proteins in Mammalian Cells
  申请人：Zhang Zhiwen

  公开号：US20120282626A1

  公开（公告）日：2012-11-08

  This invention provides methods and compositions for incorporation of an unnatural amino acid into a peptide using an orthogonal aminoacyl tRNA synthetase/tRNA pair. In particular, an orthogonal pair is provided to incorporate 5-hydroxy-L-tryptophan in a position encoded by an opal mutation.