(R)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethanethiol anion | 80888-58-0

• 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: (R)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethanethiol anion
• 英文别名: (4S)-4-amino-N-[(2R)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2-yl]-5-hydroxy-5-oxopentanimidate
• CAS: 80888-58-0
• 化学式: C₁₀H₁₆N₃O₆S
• 分子量: 306.32
• InChiKey: RWSXRVCMGQZWBV-WDSKDSINSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -4.5
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  160
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (R)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethanethiol anion 在 azide radical 作用下， 以 水 为溶剂， 生成 glutathione radical
  参考文献：
  名称：

  Kinetics of One-Electron Oxidation of Thiols and Hydrogen Abstraction by Thiyl Radicals from .alpha.-Amino C-H Bonds

  摘要：

  One-electron oxidation of cysteine, homocysteine, and glutathione by azide radical in alkaline solution (pH 10.5), where both the amino and the SH groups are deprotonated, has been investigated by pulse radiolysis. Reducing alpha-aminoalkyl radicals ((.)CR), which are formed via intramolecular rearrangement of thiyl radicals, were detected using methylviologen as oxidant in the kinetic analysis. The general scheme of the reactions is sketched. Thiyl radicals either equilibrate with RSSR(.-) in reaction 5, RS(.) + RS(-) = RSSR(.-), or undergo intramolecular transformation via equilibrium 6, RS(.) = (.)CR. At pH 10.5, equilibrium 6 is completely shifted to the right, resulting in alpha-aminoalkyl radical formation. The rate constants in the reaction scheme for cysteine, homocysteine, and glutathione were measured. With the rate constants obtained, the decay kinetics of RSSR(.-) into (.)CR was simulated, and it agreed with that measured at 420 nm. At pH 10.5, the first-order rate constants for the transformation (k(6)) were determined to be 2.5 x 10(4), 1.8 x 10(5) and 2.2 x 10(5) s(-1) for cysteine, homocysteine, and glutathione, respectively. The rate constants for intermolecular hydrogen abstraction by thiyl radicals from alpha-amino C-H bonds of alanine and glycine were determined at the same pH to be 7.7 x 10(5) and 3.2 x 10(5) M(-1) s(-1), respectively. Thermodynamic estimation places the reduction potential E degrees(H2NC(CO2-)CH3)(.), H+/H2NCH(CO2-)CH3) at ca. 1.22 V, which implies a rather weak tertiary C-H bond in the anion of alpha-amino acids. Thus, an intramolecular hydrogen abstraction mechanism for the transformation of thiyl radical to alpha-amino carbon-centered radical is postulated. Molecular geometry plays an important part in deciding the transformation rates (k(6)) of different thiyl radicals.

  DOI：

  10.1021/ja00105a048
• 作为产物：
  描述：

  (4R)-(S-glutathionyl)-4-phenyl-2-butanone 在 sodium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 生成 (R)-2-((S)-4-Amino-4-carboxy-butyrylamino)-2-(carboxymethyl-carbamoyl)-ethanethiol anion 、 苄叉丙酮
  参考文献：
  名称：

  μ谷胱甘肽转移酶类对麦克尔逆反应的立体选择性催化。活动站点中产品内部分发的后果。

  摘要：

  谷胱甘肽（GSH）与反式4-苯基-3-丁烯-2-酮（PBO）的反应在水溶液中很容易逆转，在pH 8下的表观（pH依赖）平衡常数为6.4 x 10（2） M-1。来自大鼠（M1-1和M2-2）的GSH转移酶的两类mu同工酶和两个位点特异性突变体（M1-1 / V9I和M2-2 / I9V）催化向PBO中添加GSH以及从GBO中消除GSH。 4-（S-谷胱甘肽）-4-苯基-2-丁酮的两种非对映异构产物（异构体A和B），具有不同程度的效率和立体选择性，加成反应中的主要动力学产物（异构体A）是优选的底物用于消除反应。使用产物异构体A和B的加成反应的动力学立体选择性和消除反应的稳态动力学用于估计内部立体化学平衡常数，其中产物异构体B占主导。该结果与在过量酶的条件下测得的内部平衡常数一致。结果可用于构建酶催化反应中中心配合物相互转化的反应坐标图。讨论了向α，β-不饱和羰基化合物中添加GSH的可逆性的可

  DOI：

  10.1021/tx00046a012

文献信息

• Competition between Glutathione and Guanine for a Ruthenium(II) Arene Anticancer Complex: Detection of a Sulfenato Intermediate
  作者：Fuyi Wang、Jingjing Xu、Abraha Habtemariam、Juraj Bella、Peter J. Sadler

  DOI：10.1021/ja053387k

  日期：2005.12.1

  anticancer complex [(eta6-bip)Ru(en)Cl]+ (1; bip = biphenyl, en = ethylenediamine) selectively binds to guanine (N7) bases of DNA (Novakova, O.; Chen, H.; Vrana, O.; Rodger, A.; Sadler, P. J.; Brabec, V. Biochemistry 2003, 42, 11544-11554). In this work, competition between the tripeptide glutathione (gamma-L-Glu-L-Cys-Gly; GSH) and guanine (as guanosine 3',5'-cyclic monophosphate, cGMP) for complex 1 was

  有机金属抗癌复合物 [(eta6-bip)Ru(en)Cl]+ (1；bip = 联苯，en = 乙二胺) 选择性地与 DNA 的鸟嘌呤 (N7) 碱基结合 (Novakova, O.; Chen, H.; Vrana , O.; Rodger, A.; Sadler, PJ; Brabec, V. Biochemistry 2003, 42, 11544-11554)。在这项工作中，三肽谷胱甘肽（γ-L-Glu-L-Cys-Gly；GSH）和鸟嘌呤（如鸟苷 3',5'-环磷酸酯，cGMP）对复合物 1 的竞争使用 HPLC、LC- MS 和 1H,15N NMR 光谱。在无缓冲溶液（pH 值约 3）中，1 与 GSH 的反应产生三种中间体：S-结合的硫醇合加合物 [(eta6-bip)Ru(en)(GS-S)] (4) 和两个羧酸盐结合型谷胱甘肽产物 [(eta6-bip)Ru(en)(GSH-O)]+
• Biosynthesis of 14,15-Hepoxilins in Human L1236 Hodgkin Lymphoma Cells and Eosinophils
  作者：Åsa Brunnström、Mats Hamberg、William J. Griffiths、Bengt Mannervik、Hans-Erik Claesson

  DOI：10.1007/s11745-010-3485-1

  日期：2011.1

  regioisomers formed by the 15‐LO pathway in human cells. The Hodgkin lymphoma cell line L1236 possesses high 15‐lipoxygenase‐1 (15‐LO‐1) activity and incubation of L1236 cells with arachidonic acid led to the formation of 11(S)‐hydroxy‐14(S),15(S)‐epoxy 5(Z),8(Z),12(E) eicosatrienoic acid (14,15‐HxA3 11(S)) and 13(R)‐hydroxy‐14(S),15(S)‐epoxy 5(Z),8(Z),11(Z) eicosatrienoic acid (14,15‐HxB3 13 (R)). In

  Hepoxilins是通过12-脂氧合酶（12-LO）途径在动物细胞中合成的环氧醇。表皮是人类苏木素的主要来源。在这里，我们报道了由人体内15-LO途径形成的新型Hexixilin区域异构体的形成。霍奇金淋巴瘤细胞株L1236具有高15-脂氧合酶-1（15-LO-1）活性，L1236细胞与花生四烯酸的孵育导致11（S）-hydroxyl -14（S），15（S）的形成-环氧5（Z），8（Z），12（E）二十碳三烯酸（14,15-HxA 3 11（S））和13（R）-羟基-14（S），15（S）-环氧5（Z），8（Z），11（Z）二十碳三烯酸（14,15-HxB 3 13（R））。此外，还检测到两个迄今未鉴定的产物，并通过阳离子电喷雾串联质谱法对其进行了收集和分析。这些代谢物被鉴定为11（S），15（S）-二羟基-14（R）-谷胱甘肽-5（Z），8（Z），12（E）-二十碳三烯酸（14,15-HxA
• S-Glutathionyl-(chloro)hydroquinone reductases: a novel class of glutathione transferases
  作者：Luying Xun、Sara M. Belchik、Randy Xun、Yan Huang、Huina Zhou、Emiliano Sanchez、ChulHee Kang、Philip G. Board

  DOI：10.1042/bj20091863

  日期：2010.6.15

  Sphingobium chlorophenolicum completely mineralizes PCP (pentachlorophenol). Two GSTs (glutathione transferases), PcpC and PcpF, are involved in the degradation. PcpC uses GSH to reduce TeCH (tetrachloro-p-hydroquinone) to TriCH (trichloro-p-hydroquinone) and then to DiCH (dichloro-p-hydroquinone) during PCP degradation. However, oxidatively damaged PcpC produces GS-TriCH (S-glutathionyl-TriCH) and GS-DiCH (S-glutathionyl-TriCH) conjugates. PcpF converts the conjugates into TriCH and DiCH, re-entering the degradation pathway. PcpF was further characterized in the present study. It catalysed GSH-dependent reduction of GS-TriCH via a Ping Pong mechanism. First, PcpF reacted with GS-TriCH to release TriCH and formed disulfide bond between its Cys53 residue and the GS moiety. Then, a GSH came in to regenerate PcpF and release GS–SG. A TBLASTN search revealed that PcpF homologues were widely distributed in bacteria, halobacteria (archaea), fungi and plants, and they belonged to ECM4 (extracellular mutant 4) group COG0435 in the conserved domain database. Phylogenetic analysis grouped PcpF and homologues into a distinct group, separated from Omega class GSTs. The two groups shared conserved amino acid residues, for GSH binding, but had different residues for the binding of the second substrate. Several recombinant PcpF homologues and two human Omega class GSTs were produced in Escherichia coli and purified. They had zero or low activities for transferring GSH to standard substrates, but all had reasonable activities for GSH-dependent reduction of disulfide bond (thiol transfer), dehydroascorbate and dimethylarsinate. All the tested PcpF homologues reduced GS-TriCH, but the two Omega class GSTs did not. Thus PcpF homologues were tentatively named S-glutathionyl-(chloro)hydroquinone reductases for catalysing the GSH-dependent reduction of GS-TriCH.

  Sphingobium chlorophenolicum 能完全矿化五氯苯酚。两种谷胱甘肽转移酶（GST），即 PcpC 和 PcpF 参与了降解过程。在五氯苯酚降解过程中，PcpC 利用 GSH 将 TeCH（四氯对苯二酚）还原为 TriCH（三氯对苯二酚），然后还原为 DiCH（二氯对苯二酚）。然而，受到氧化损伤的 PcpC 会产生 GS-TriCH（S-谷氨酰-三氢苯酚）和 GS-DiCH（S-谷氨酰-三氢苯酚）共轭物。PcpF 将这些共轭物转化为 TriCH 和 DiCH，重新进入降解途径。本研究对 PcpF 进行了进一步鉴定。它通过乒乓机制催化 GSH 依赖性还原 GS-TriCH。首先，PcpF 与 GS-TriCH 反应，释放出 TriCH，并在其 Cys53 残基与 GS 分子之间形成二硫键。然后，GSH 进入，再生 PcpF 并释放 GS-SG。TBLASTN检索发现，PcpF同源物广泛分布于细菌、卤杆菌（古细菌）、真菌和植物中，在保守结构域数据库中属于ECM4（细胞外突变体4）组COG0435。系统发生分析将 PcpF 及其同源物归入一个不同的组，与 Omega 类 GST 区分开来。这两个组在与 GSH 结合时共享保守氨基酸残基，但在与第二种底物结合时有不同的残基。在大肠杆菌中生产并纯化了几种重组 PcpF 同源物和两种人类 Omega 类 GST。它们将 GSH 转移到标准底物的活性为零或较低，但在依赖 GSH 的二硫键还原（硫醇转移）、脱氢抗坏血酸和二甲基胂酸方面都有合理的活性。所有测试的 PcpF 同源物都能还原 GS-三羟甲基丙烷，但两种欧米茄类 GSTs 却不能。因此，PcpF 同源物被暂时命名为 S-谷胱甘肽-（氯）对苯二酚还原酶，用于催化 GSH 依赖性还原 GS-TriCH。
• Compared Reactivities of Trypanothione and Glutathione in Conjugation Reactions.
  作者：Mireille MOUTIEZ、Djalal MEZIANE-CHERIF、Marc AUMERCIER、Christian SERGHERAERT、Andre TARTAR

  DOI：10.1248/cpb.42.2641

  日期：——

  In order to compare the non-enzymatic capacities of the xenobiotic conjugation of trypanothione (a spermidine-glutathione conjugate unique to kinetoplastidae) and glutathione, the reactivity of their respective thiols was investigated. The acido-basic properties of both compounds and their nucleophilicity toward Elliman's reagent and 1-chloro-2, 4-dinitrobenzene were studied. Our results show that although glutathione is a better nucleophile than trypanothione, the latter is more reactive because it is more ionized in a large pH range. This pH range likely includes the pH to which such conjugation reactions are expected to happen in vivo. Thus, the better conjugation capacity of trypanothione could make it the cornerstone for the xenobiotic detoxication of trypanosomatidae.

  为了比较胰硫蛋白（一种奇睾酮科特有的精胺-谷胱甘肽共轭物）和谷胱甘肽的异生物共轭的非酶能力，研究了它们各自硫醇的反应性。研究了这两种化合物的酸碱性质及其对埃利曼试剂和 1-氯-2，4-二硝基苯的亲核性。我们的研究结果表明，虽然谷胱甘肽的亲核性优于胰硫蛋白，但后者的反应性更强，因为它在较大的 pH 值范围内电离程度更高。这个 pH 值范围很可能包括预计在体内会发生这种共轭反应的 pH 值。因此，胰硫磷的共轭能力更强，可使其成为锥虫解毒的基石。
• The sulfane sulfur of persulfides is the actual substrate of the sulfur-oxidizing enzymes from Acidithiobacillus and Acidiphilium spp.
  作者：Thore Rohwerder、Wolfgang Sand

  DOI：10.1099/mic.0.26212-0

  日期：2003.7.1

  found in crude extracts. All cell-free systems oxidized elemental sulfur only via glutathione persulfide (GSSH), a non-enzymic reaction product from glutathione (GSH) and elemental sulfur. Thus, GSH plays a catalytic role in elemental sulfur activation, but is not consumed during enzymic sulfane sulfur oxidation. Sulfite is the first product of sulfur dioxygenase activity; it further reacted non-enzymically

  为了鉴定中酸性嗜酸性嗜酸硫硫杆菌硫氧化酶菌株DSM 504和K6的谷胱甘肽-依赖性硫双加氧酶（EC 1.13.11.18）元素硫氧化的实际底物，分析了酸性嗜氧硫杆菌铁氧体菌株R1和嗜酸性嗜酸杆菌DSM 700。在粗提取物中发现了高达460 nmol x min（-1）（mg蛋白）（-1）的高比硫双加氧酶活性。所有无细胞系统仅通过谷胱甘肽过硫化物（GSSH）来氧化元素硫，GSH是谷胱甘肽（GSH）和元素硫的非酶反应产物。因此，GSH在元素硫的活化中起催化作用，但在酶法硫烷硫氧化过程中不被消耗。亚硫酸盐是硫双加氧酶活性的第一个产物。它进一步非酶促地与硫酸盐反应，硫代硫酸盐或谷胱甘肽S-磺酸盐（GSSO（-3））。游离的硫化物未被硫双加氧酶氧化。过硫醚作为硫供体不能用其他含硫烷硫的化合物（硫代硫酸盐，多硫代酸盐，双有机基多硫烷或单芳基硫代磺酸盐）代替。通过双加氧酶氧化H（2）S需要GSSG，即G