5-S-半胱氨酰多巴胺 | 99558-89-1

• 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
• 中文名称: 5-S-半胱氨酰多巴胺
• 英文名称: 5-S-cysteinyldopamine
• 英文别名: 5-cysteinyl-dopamine；(2R)-2-amino-3-[5-(2-aminoethyl)-2,3-dihydroxyphenyl]sulfanylpropanoic acid
• CAS: 99558-89-1
• 化学式: C₁₁H₁₆N₂O₄S
• 分子量: 272.325
• InChiKey: BZYHBWCVRKSWDB-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  155
• 氢给体数：
  5
• 氢受体数：
  7

安全信息

• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  5-S-半胱氨酰多巴胺 以 phosphate buffer 为溶剂， 生成 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid
  参考文献：
  名称：

  Influence of glutathione on the oxidation chemistry of 5-S-cysteinyldopamine: potentially neuroprotective reactions of relevance to Parkinson's disease

  摘要：

  In recent reports from this laboratory we have hypothesized that a key step underlying the degeneration of pigmented dopaminergic neurons in the substantia nigra pars compacta (SNc) in Parkinson's disease is an accelerated rate of oxidation of intraneuronal dopamine in the presence of L-cysteine (CySH) to form initially 5-S-cysteinyldopamine (5-S-CyS-DA). 5-S-CyS-DA, however, is more easily oxidized than dopamine in a reaction which leads to the dihydrobenzothiazine (DHBT) 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-1), a putative endogenously-formed metabolite that may be responsible for inhibition of mitochondrial complex I and alpha -ketoglutarate dehydrogenase, characteristic defects in the parkinsonian SNc. In this investigation it is demonstrated that glutathione (GSH) dramatically attenuates the oxidative transformation of 5-S-CyS-DA into DHBT-1 by two major pathways. In one pathway GSH displaces the cysteinyl residue from the o-quinone proximate oxidation product of 5-S-CyS-DA forming the corresponding glutathionyl conjugate that is attacked by GSH, to form 2,5-di-S-glutathionyldopamine, or by released CySH to give 2-S-cysteinyl-5-S-glutathionyldopamine. The former is the precursor of 2,5,6-tris-S-glutathionyldopamine, a major reaction product. However, intramolecular cyclization of the o-quinone proximate product of 2-S-cysteinyl-5-S-glutathionyldopamine is the first step in a pathway leading to glutathionyl conjugates of 8-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-5). The second pathway involves nucleophilic addition of GSH to the o-quinone proximate oxidation product of 5-S-CyS-DA forming 2-S-glutathionyl-5-S-cysteinyldopamine the precursor of a number of glutathionyl conjugates of DHBT-1. These results raise the possibility that strategies which elevate intraneuronal levels of GSH in dopaminergic SNc cells in Parkinson's disease patients may block formation of the putative mitochondrial toxin DHBT-1 and hence be neuroprotective. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00953-4
• 作为产物：
  描述：

  盐酸多巴胺 在 盐酸 作用下， 以 盐酸 为溶剂， 反应 0.5h， 生成 5-S-半胱氨酰多巴胺
  参考文献：
  名称：

  进一步了解L-半胱氨酸对多巴胺氧化化学的影响：与帕金森氏病潜在相关的反应途径。

  摘要：

  神经黑色素（一种通常在黑质（SN）的多巴胺能细胞体细胞质中发现的黑色聚合色素）的形成的第一步是将多巴胺（DA）自动氧化为DA-o-醌（1）。在这项研究中，证明了在存在L-半胱氨酸（CySH）的情况下，邻醌1会被清除，生成5-S-半胱氨酰多巴胺（5-S-Cys-DA，主要产品）和2-S-半胱氨酰多巴胺（ 2-S-CyS-DA，次要产品）。这些半胱氨酰缀合物比DA更容易被氧化。所得产物的相对产率取决于游离CySH的浓度。这些产品包括2,5-双-S-半胱氨酸多巴胺（2,5-bi-S-CyS-DA）和2,5,6-三-S-半胱氨酰多巴胺（2,5,6-三-S-CyS-DA DA），7-（2-氨基乙基）-3,4-二氢-5-羟基-2H-1,4-苯并噻嗪-3-羧酸（DHBT-1），8-（2-氨基乙基）-3,4 -二氢-5-羟基-2H-1 4-苯并噻嗪-3-羧酸（DHBT-5），以及这些二氢苯并噻嗪（DHBT）的许多半胱氨酸共轭物。当将2

  DOI：

  10.1021/tx960008f

文献信息

• Effects of L-Cysteine on the Oxidation Chemistry of Dopamine: New Reaction Pathways of Potential Relevance to Idiopathic Parkinson's Disease
  作者：Fa Zhang、Glenn Dryhurst

  DOI：10.1021/jm00034a006

  日期：1994.4

  Oxidation of the catecholaminergic neurotransmitter dopamine (1) at physiological pH normally results in formation of black, insoluble melanin polymer. In this study, it is demonstrated that L-cysteine (CySH) can divert the melanin pathway by scavenging the proximate o-quinone oxidation product of 1 to give 5-S-cysteinyldopamine (8). This cysteinyl conjugate is further oxidized in the presence of free

  儿茶酚胺能神经递质多巴胺（1）在生理pH值下的氧化通常会导致形成黑色的不溶性黑色素聚合物。在这项研究中，证明了L-半胱氨酸（CySH）可以通过清除1的邻苯二酚近邻氧化产物而转移黑色素途径，从而生成5-S-半胱氨酰多巴胺（8）。该半胱氨酰共轭物在游离CySH的存在下进一步氧化，得到7-（2-氨基乙基）-3,4-二氢-5-羟基-2H-1,4-苯并噻嗪-3-羧酸（11）及其6除许多其他未知化合物外，-S-半胱氨酰（12），8-S-半胱氨酰（14）和6,8-二-S-半胱氨酰（16）偶联物。5-S-半胱氨酰多巴胺（8）和二氢苯并噻嗪11、12、14和16都比1更容易被氧化。随着CySH摩尔过量的增加，黑色素的形成减少，最终，完全被封锁。初步实验表明，当将二氢苯并噻嗪11及其半胱氨酰结合物12和14注入实验室小鼠的大脑时，它们具有致命性，并引起深刻的行为反应，包括活动过度和震颤。基于这些结果和最近的其
• Oxidation of Dopamine in the Presence of Cysteine:  Characterization of New Toxic Products
  作者：Xue-Ming Shen、Fa Zhang、Glenn Dryhurst

  DOI：10.1021/tx960145c

  日期：1997.2.1

  = 1.5 microgram) are lethal when administered into the brains of mice and evoke hyperactivity and tremor. The potential relevance of the in vitro chemistry described in this and earlier reports to reaction that might occur in neuromelanin-pigmented dopaminergic neurons in Parkinson's disease is discussed.

  先前的研究表明，在pH 7.4的L-半胱氨酸（CySH）存在下，多巴胺（DA）的氧化产生了神经递质的半胱氨酰共轭物的复杂混合物，该混合物很容易被进一步氧化为许多二氢苯并噻嗪（DHBT）以及未知的黄色产品。在这项调查中，已经确定了其中三种产品。5-S-半胱氨酰多巴胺（5-S-CyS-DA）和7的氧化反应生成7-（2氨基乙基）-5-羟基-1,4-苯并噻嗪-3-羧酸（BT-1） -（2-氨基乙基）-3,4-二氢-5-羟基-2H-1,4-苯并噻嗪-3-羧酸（DHBT-1）。区域异构体6-（2-氨基乙基）-1,8,9,10-四氢苯并[1,2-b：4,3-b']双[1,4]噻嗪-9-羧酸（12）和6- （2-氨基乙基）-1,2,3,10-四氢苯并[1,2-b：4,3-b']双[1,4]噻嗪-2-羧酸（13）是通过2的氧化而形成的，5-bi-S-CyS-DA），6-S-半胱氨酰基-7-（2-氨基乙基）-
• Kinetic evidence that cysteine reacts with dopaminoquinone via reversible adduct formation to yield 5-cysteinyl-dopamine: an important precursor of neuromelanin
  作者：Guy N. L. Jameson、Jie Zhang、Reginald F. Jameson、Wolfgang Linert

  DOI：10.1039/b316294j

  日期：——

  magnitude (K(cys)=(1.09 +/- 0.02 x 10(-3); K(1,maa)=(7.45 +/- 0.11 x 10(-3)). (Note that the possibility that cys also forms a bis-complex at much higher cys concentrations cannot be excluded.) The rates of decomposition differ markedly-the cys complex has the value k(cys)= 1830 +/- 50 s(-1) whereas the rate constant for the decomposition of the maa complex is k(maa)= 69.3 +/- 0.02 s(-1) and we attribute

  半胱氨酸（cys）与多巴氨基醌（DQ）形成（主要）5-半胱氨酰-多巴胺（5-cys-DA）的反应是令人感兴趣的，因为已知其在哺乳动物脑中黑色素的产生中起作用。为了深入了解这一重要反应，进行了体外详细的动力学研究。已经确定cys通过中间加合物或配合物的初始可逆形成与DQ反应，然后该加合物分解形成5-cys-DA。几乎可以肯定同时形成了一个少量的2-cys-DA，但无法对其动力学进行研究。通过使DQ与cys类似物巯基乙酸（maa）反应，有助于动力学数据的澄清。发现Maa以类似的方式发生反应，但也可逆地形成双复合物。这个双复数，2 5-（maa）（2）-多巴氨基醌与双质子化化合物处于平衡状态，但是在这些动力学研究中所用的时间范围内，这两种物质均未发生进一步反应。从数据中提取了平衡常数和一阶速率常数，发现半胱氨酸复合物比其maa类似物弱一个数量级（K（cys）=（1.09 +/- 0.02 x 10（-3）
• Reactions of Cysteine and Cysteinyl Derivatives with Dopamine-o-quinone and Further Insights into the Oxidation Chemistry of 5-S-Cysteinyldopamine: Potential Relevance to Idiopathic Parkinson′s Disease
  作者：F. Zhang、G. Dryhurst

  DOI：10.1006/bioo.1995.1016

  日期：1995.9

  Recent studies suggest that elevated rates of autoxidation of dopamine (DA) in the cytoplasm of neuromelanin-pigmented dopaminergic cell bodies in the substantia nigra (SN) and/or reactions of its proximate oxidation product, DA-o-quinone, with glutathione (GSH) or L-cysteine (CySH) might yield endotoxins that play roles in the pathogenesis of idiopathic Parkinson's Disease (PD). In this study the reactions between DA-o-quinone and CySH and some cysteine derivatives have been studied. The reactions between DA-o-quinone and CySH or cysteine methyl ester are rapid and give the corresponding 5-S-cysteinyl conjugates of DA as the predominant products. By contrast, the reaction between the sterically hindered D-penicillamine methyl ester (PME) and DA-o-quinone is much slower to give, initially, a mixture of the 2-S-, 5-S-, and 6-S-PME conjugates of DA. These conjugates are then further oxidized by unreacted DA-o-quinone to give a complex mixture of products which include 7-(2-aminoethyl)-5-hydroxy-2,2-dimethyl-1,4-benzothiazine-3-carboxylic acid methyl ester (13). Large increases in the 5-S-cysteinyldopamine (5-S-CyS-DA)/DA concentration ratio have been measured in the Parkinsonian SN and have been interpreted to reflect elevated rates of DA autoxidation in this structure that degenerates in PD. However, the present study reveals that at physiological pH 5-S-CyS-DA is not only more easily oxidized than DA but a bicyclic o-quinone imine (5) intermediate is formed that can chemically oxidize the former conjugate in a reaction that leads to 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (6). Compound 6 is lethal when administered into the brains of mice. However, this putative dihydrobenzothiazine endotoxin is even more easily oxidized than 5-S-CyS-DA in a rather complex reaction that ultimately forms 7-(2-aminoethyl)-5-hydroxy-1,4-benzothiazine-3-carboxylic acid (15). Although this benzothiazine could not be isolated it was identified by comparison of its electrochemical and spectroscopic properties in solution with those of 13. The results of this study suggest that benzothiazine 15 might serve as a better analytical marker molecule than 5-S-CyS-DA for either elevated rates of DA autoxidation and/or for roles of GSH and CySH in the neurodegenerative mechanisms in the SN that contribute to PD. (C) 1995 Academic Press, Inc.
• Further Insights into the Influence of <scp>l</scp>-Cysteine on the Oxidation Chemistry of Dopamine:  Reaction Pathways of Potential Relevance to Parkinson's Disease
  作者：Xue-Ming Shen、Glenn Dryhurst

  DOI：10.1021/tx960008f

  日期：1996.1.1

  normally found in the cytoplasm of dopaminergic cell bodies in the substantia nigra (SN), is the autoxidation of dopamine (DA) to DA-o-quinone (1). In this investigation, it is demonstrated that in the presence of L-cysteine (CySH) o-quinone 1 is scavenged to give 5-S-cysteinyldopamine (5-S-Cys-DA, major product) and 2-S-cysteinyldopamine (2-S-CyS-DA, minor product). These cysteinyl conjugates are more easily

  神经黑色素（一种通常在黑质（SN）的多巴胺能细胞体细胞质中发现的黑色聚合色素）的形成的第一步是将多巴胺（DA）自动氧化为DA-o-醌（1）。在这项研究中，证明了在存在L-半胱氨酸（CySH）的情况下，邻醌1会被清除，生成5-S-半胱氨酰多巴胺（5-S-Cys-DA，主要产品）和2-S-半胱氨酰多巴胺（ 2-S-CyS-DA，次要产品）。这些半胱氨酰缀合物比DA更容易被氧化。所得产物的相对产率取决于游离CySH的浓度。这些产品包括2,5-双-S-半胱氨酸多巴胺（2,5-bi-S-CyS-DA）和2,5,6-三-S-半胱氨酰多巴胺（2,5,6-三-S-CyS-DA DA），7-（2-氨基乙基）-3,4-二氢-5-羟基-2H-1,4-苯并噻嗪-3-羧酸（DHBT-1），8-（2-氨基乙基）-3,4 -二氢-5-羟基-2H-1 4-苯并噻嗪-3-羧酸（DHBT-5），以及这些二氢苯并噻嗪（DHBT）的许多半胱氨酸共轭物。当将2