2-acetyl-5,5-dimethyl-thiazolidine-4-carboxylic 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-acetyl-5,5-dimethyl-thiazolidine-4-carboxylic acid
• 英文别名: (4S)-2-acetyl-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid
• 化学式: C₈H₁₃NO₃S
• 分子量: 203.262
• InChiKey: OEXVGWYPLIAWAV-ZBHICJROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  D-青霉胺 、 丙酮醛 以 phosphate buffer 为溶剂， 反应 24.0h， 生成 2-acetyl-5,5-dimethyl-thiazolidine-4-carboxylic acid
  参考文献：
  名称：

  Identification of α-dicarbonyl scavengers for cellular protection against carbonyl stress

  摘要：

  Tissue deterioration and aging have long been associated with the accumulation of chemically induced protein and DNA damage. Reactive oxygen species (ROS) and reactive carbonyl species (RCS), especially alpha-dicarbonyl compounds, are key mediators of damage caused by oxidative stress, glycation, and UV-irradiation. The toxic effects of ROS are counteracted in vivo by antioxidants and antioxidant enzymes, and the deleterious effects of one RCS, methylglyoxal, are counteracted by a ubiquitous glyoxalase system. Carbonyl stress as a result of toxic effects of various mono-dicarbonyls (e.g. 4-hydroxynonenal) and alpha-dicarbonyls (e.g. glyoxal and deoxyosones) cannot be directly antagonized by antioxidants, and only a small number of biological carbonyl scavengers like glutathione (GSH) have been identified to date. We have developed a new screening method for the identification of carbonyl scavengers using a rapid glycation system that proceeds independent of oxygen and therefore, excludes identification of inhibitory compounds acting as antioxidants. Using this screening assay adapted to 96-well microtiter plates, we have identified the cysteine derivative 3,3,3-dimethyl-D-cysteine as a potent inhibitor of non-oxidative advanced glycation. Comparative kinetic analyses demonstrated the superior alpha-oxoaldchyde-scavenging activity Of D-penicillamine over that of aminoguanidine. D-Penicillamine traps alpha-oxoaldehydes by forming a 2-acylthiazolidine derivative as shown by structure elucidation of reaction products between D-penicillamine and methylglyoxal or phenylglyoxal, We demonstrated that upon co-incubation, D-penicillamine protects human skin keratinocytes and fibroblasts (CF3 cells) against glyoxal- and methylglyoxal-induced carbonyl toxicity. Our research qualifies alpha-amino-beta-mercapto-beta,beta-dimethyl-ethane as a promising pharmacophore for the development of related alpha-dicarbonyl scavengers as therapeutic agents to protect cells against carbonyl stress. (C) 2002 Published by Elsevier Science Inc.

  DOI：

  10.1016/s0006-2952(01)00915-7

文献信息

• METHODS OF QUANTIFYING N2-(1-CARBOXYETHYL)-2'-DEOXY-GUANOSINE (CEdG) AND SYNTHESIS OF OLIGONUCLEOTIDES CONTAINING CEdG
  申请人：Rahbar Samuel

  公开号：US20100102218A1

  公开（公告）日：2010-04-29

  Methods of quantifying a N 2 -carboxyethyl-2′-deoxyguanosine (CEdG) levels in biological samples and comparing those levels to known normal levels can diagnose a number of disorders, including diabetes and cancer. Methods can also determine whether therapies for disorders are effective by measuring CEdG levels before and after treatment. Measurement of CEdG levels occurs using liquid chromatography electrospray ionization tandem mass spectrometry.
• Identification of α-dicarbonyl scavengers for cellular protection against carbonyl stress
  作者：Georg T. Wondrak、Daniel Cervantes-Laurean、Michael J. Roberts、Jaber G. Qasem、Moonsun Kim、Elaine L. Jacobson、Myron K. Jacobson

  DOI：10.1016/s0006-2952(01)00915-7

  日期：2002.2

  Tissue deterioration and aging have long been associated with the accumulation of chemically induced protein and DNA damage. Reactive oxygen species (ROS) and reactive carbonyl species (RCS), especially alpha-dicarbonyl compounds, are key mediators of damage caused by oxidative stress, glycation, and UV-irradiation. The toxic effects of ROS are counteracted in vivo by antioxidants and antioxidant enzymes, and the deleterious effects of one RCS, methylglyoxal, are counteracted by a ubiquitous glyoxalase system. Carbonyl stress as a result of toxic effects of various mono-dicarbonyls (e.g. 4-hydroxynonenal) and alpha-dicarbonyls (e.g. glyoxal and deoxyosones) cannot be directly antagonized by antioxidants, and only a small number of biological carbonyl scavengers like glutathione (GSH) have been identified to date. We have developed a new screening method for the identification of carbonyl scavengers using a rapid glycation system that proceeds independent of oxygen and therefore, excludes identification of inhibitory compounds acting as antioxidants. Using this screening assay adapted to 96-well microtiter plates, we have identified the cysteine derivative 3,3,3-dimethyl-D-cysteine as a potent inhibitor of non-oxidative advanced glycation. Comparative kinetic analyses demonstrated the superior alpha-oxoaldchyde-scavenging activity Of D-penicillamine over that of aminoguanidine. D-Penicillamine traps alpha-oxoaldehydes by forming a 2-acylthiazolidine derivative as shown by structure elucidation of reaction products between D-penicillamine and methylglyoxal or phenylglyoxal, We demonstrated that upon co-incubation, D-penicillamine protects human skin keratinocytes and fibroblasts (CF3 cells) against glyoxal- and methylglyoxal-induced carbonyl toxicity. Our research qualifies alpha-amino-beta-mercapto-beta,beta-dimethyl-ethane as a promising pharmacophore for the development of related alpha-dicarbonyl scavengers as therapeutic agents to protect cells against carbonyl stress. (C) 2002 Published by Elsevier Science Inc.