2-amino-5-(1-(carboxymethylamino)-3-(4-hydroxybenzylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acid

• 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-amino-5-(1-(carboxymethylamino)-3-(4-hydroxybenzylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acid
• 英文别名: (-)-γ-L-glutamyl-L-[S-(4-hydroxybenzyl)]cysteinylglycine；4-(hydroxymethyl)phenol-glutathione conjugate；S-(4-hydroxybenzyl)glutathione；(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[(4-hydroxyphenyl)methylsulfanyl]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
• 化学式: C₁₇H₂₃N₃O₇S
• 分子量: 413.452
• InChiKey: GZQWDMACVJFPRW-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  204
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-amino-5-(1-(carboxymethylamino)-3-(4-hydroxybenzylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acid 在 sodium tetrahydroborate 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 1.17h， 生成 (-)-γ-L-[N-(4-hydroxybenzyl)]glutamyl-L-[S-(4-hydroxybenzyl)]cysteinylglycine
  参考文献：
  名称：

  4-Hydroxybenzyl-substituted glutathione derivatives fromGastrodia elata

  摘要：

  Seven new 4-hydroxybenzyl-substituted glutathione derivatives (2-8), together with a known analogue (1), were isolated from the aqueous extract of Gastrodia elata Blume rhizomes. Their structures were determined by using spectroscopic and chemical methods. The absolute configurations of 1-8 were assigned by using Marfey's method, combined with comparing the NMR and CD spectroscopic data of sulfoxide moieties in 3-6 with those of S-(4-hydroxybenzyl)cysteine sulfoxide stereoisomers (9-12) synthesized as authentic samples. The configurations of 9-12 were confirmed by electronic CD calculations based on the quantum-mechanical time-dependent density functional theory. Furthermore, the structures of 1, 3, 5, 7, and 8 were verified by synthesis. Compound 3 was active against serum deprivation-induced PC12 cell damage and synthetic 9-14 exhibited activity against Fe2+-cysteine induced rat liver microsomal lipid peroxidation.

  DOI：

  10.1080/10286020.2015.1040000
• 作为产物：
  描述：

  4-乙酰氧基苄醇 在 吡啶 、 disodium hydrogenphosphate 、 sodium dihydrogenphosphate 、 氯化亚砜 作用下， 以 重水 、 甲苯 为溶剂， 反应 73.0h， 生成 2-amino-5-(1-(carboxymethylamino)-3-(4-hydroxybenzylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acid
  参考文献：
  名称：

  Chemical Insights in the Concept of Hybrid Drugs:  The Antitumor Effect of Nitric Oxide-Donating Aspirin Involves A Quinone Methide but Not Nitric Oxide nor Aspirin

  摘要：

  Hybrid drug 1 (NO-ASA) continues to attract intense research from chemists and biologists alike. It consists of ASA and a -ONO2 group connected through a spacer and is in preclinical development as an antitumor drug. We report that, contrary to current beliefs, neither ASA nor NO contributes to this antitumor effect. Rather, an unsubstituted QM was identified as the sole cytotoxic agent. QM forms from 1 after carboxylic ester hydrolysis and, in accordance with the HSAB theory, selectively reacts with cellular GSH, which in turn triggers cell death. Remarkably, a derivative lacking ASA and the -ONO2 group is 10 times more effective than 1. Thus, our data provide a conclusive molecular mechanism for the antitumor activity of 1. Equally importantly, we show for the first time that a "presumed invisible" linker in a hybrid drug is not so invisible after all and is in fact solely responsible for the biological effect.

  DOI：

  10.1021/jm061371e

文献信息

• Chemical Insights in the Concept of Hybrid Drugs:  The Antitumor Effect of Nitric Oxide-Donating Aspirin Involves A Quinone Methide but Not Nitric Oxide nor Aspirin
  作者：Niels Hulsman、Jan Paul Medema、Carina Bos、Aldo Jongejan、Rob Leurs、Martine J. Smit、Iwan J. P. de Esch、Dick Richel、Maikel Wijtmans

  DOI：10.1021/jm061371e

  日期：2007.5.1

  Hybrid drug 1 (NO-ASA) continues to attract intense research from chemists and biologists alike. It consists of ASA and a -ONO2 group connected through a spacer and is in preclinical development as an antitumor drug. We report that, contrary to current beliefs, neither ASA nor NO contributes to this antitumor effect. Rather, an unsubstituted QM was identified as the sole cytotoxic agent. QM forms from 1 after carboxylic ester hydrolysis and, in accordance with the HSAB theory, selectively reacts with cellular GSH, which in turn triggers cell death. Remarkably, a derivative lacking ASA and the -ONO2 group is 10 times more effective than 1. Thus, our data provide a conclusive molecular mechanism for the antitumor activity of 1. Equally importantly, we show for the first time that a "presumed invisible" linker in a hybrid drug is not so invisible after all and is in fact solely responsible for the biological effect.
• 4-Hydroxybenzyl-substituted glutathione derivatives from<i>Gastrodia elata</i>
  作者：Qing-Lan Guo、Ya-Nan Wang、Cheng-Gen Zhu、Ming-Hua Chen、Zhi-Bo Jiang、Nai-Hong Chen、Xiu-Yun Song、Mei-Jin Zhang、Jian-Gong Shi

  DOI：10.1080/10286020.2015.1040000

  日期：2015.5.4

  Seven new 4-hydroxybenzyl-substituted glutathione derivatives (2-8), together with a known analogue (1), were isolated from the aqueous extract of Gastrodia elata Blume rhizomes. Their structures were determined by using spectroscopic and chemical methods. The absolute configurations of 1-8 were assigned by using Marfey's method, combined with comparing the NMR and CD spectroscopic data of sulfoxide moieties in 3-6 with those of S-(4-hydroxybenzyl)cysteine sulfoxide stereoisomers (9-12) synthesized as authentic samples. The configurations of 9-12 were confirmed by electronic CD calculations based on the quantum-mechanical time-dependent density functional theory. Furthermore, the structures of 1, 3, 5, 7, and 8 were verified by synthesis. Compound 3 was active against serum deprivation-induced PC12 cell damage and synthetic 9-14 exhibited activity against Fe2+-cysteine induced rat liver microsomal lipid peroxidation.