N^ε-(Trichloroacetyl)-L-lysine

• 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: N^ε-(Trichloroacetyl)-L-lysine
• 英文别名: (2S)-2-amino-6-[(2,2,2-trichloroacetyl)amino]hexanoic acid
• 化学式: C₈H₁₃Cl₃N₂O₃
• 分子量: 291.562
• InChiKey: DDALUBGGQCPWJA-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  92.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  L-赖氨酸 、 三氯乙酸乙酯 在 sodium hydroxide 作用下， 反应 2.0h， 以23%的产率得到N^ε-(Trichloroacetyl)-L-lysine
  参考文献：
  名称：

  四氯环氧乙烷：水解产物以及与磷酸盐和赖氨酸的反应。

  摘要：

  四氯乙烯或四氯乙烯（PCE）具有广泛的工业用途，并且由于多种作用而具有毒理学意义。现有的大多数文献都提出PCE氧化物是PCE氧化代谢为Cl（3）CCO（2）H，草酸和与蛋白质共价结合的产物（包括赖氨酸的三氯乙酰基衍生物）的重要中间体。通过光化学氧化PCE合成并表征了PCE氧化物。在中性pH值下分解（t（1/2）= 7.9分钟在0摄氏度，23摄氏度在5.8分钟，在37摄氏度在2.6分钟）仅产生痕量（约1％）Cl（3）CCO（2）H ; 确定的主要产品为一氧化碳（产率73％）和一氧化碳（2）（产率63％）。在磷酸盐缓冲液（0.10 M）中，主要产物被鉴定为草酰磷酸酯。草酰氯还反应在水溶液中形成CO和CO（2），并在中性磷酸盐缓冲液中形成草酰磷酸。磷酸草酰在37℃分解为草酸（t（1/2）= 53分钟），但不与赖氨酸反应。PCE氧化物与游离赖氨酸的反应产生了赖氨酸加赖氨酸二聚体的草酸酰胺衍生物，其

  DOI：

  10.1021/tx020028j

文献信息

• RAPAFUCIN DERIVATIVE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：The Johns Hopkins University

  公开号：US20210094933A1

  公开（公告）日：2021-04-01

  The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

  本公开提供了受免疫蛋白配体家族FK506和雷帕霉素天然产物启发的大环化合物。生成包含FK506和雷帕霉素结合结构域的Rapafucin大环化合物库，应具有作为治疗疾病新药的潜力。
• Rapafucin derivative compounds and methods of use thereof
  申请人：The Johns Hopkins University

  公开号：US11066416B2

  公开（公告）日：2021-07-20

  The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

  本公开提供了受天然产物 FK506 和雷帕霉素的免疫嗜蛋白配体家族启发的大环化合物。由含有 FK506 和雷帕霉素结合结构域的大环化合物组成的雷帕霉素库，作为开发用于治疗疾病的药物的新线索，具有巨大的潜力。
• Immunochemical Detection of Protein Adducts in Mice Treated with Trichloroethylene
  作者：N. Christine Halmes、David C. McMillan、John E. Oatis,、Neil R. Pumford

  DOI：10.1021/tx950171v

  日期：1996.1.1

  Trichloroethylene has been shown to produce tumors in rodents and is a suspect human carcinogen. In addition, a number of case reports raise the possibility that trichloroethylene can induce an autoimmune disorder known as systemic sclerosis. To investigate whether covalent binding of reactive trichloroethylene metabolites may be involved in the mechanisms underlying these toxic responses, we have developed a polyclonal antibody that can recognize trichloroethylene-protein adducts in tissues. The antibody was prepared by immunizing a rabbit with dichloroacetic anhydride-modified keyhole limpet hemocyanin. Enzyme-linked immunosorbent assay data indicated that the serum antibody recognized dichloroacetic anhydride-modified rabbit serum albumin, but not unmodified protein. In addition, N-epsilon-dichloroacetyl-L-lysine was the most potent inhibitor of antibody binding to dichloroacetic anhydride-modified rabbit serum albumin, indicating that the antibody recognizes primarily dichloroacetylated lysine residues. Immunoblots revealed the presence of two major trichloroethylene adducts at 50 and 100 kDa in liver microsomal fractions from male B6C3/F1 mice treated with trichloroethylene. The formation of trichloroethylene adducts was both dose and time dependent. Furthermore, the 50-kDa adduct was found to comigrate on a polyacrylamide gel with cytochrome P450 2E1. These data show that reactive metabolites of trichloroethylene are formed in, vivo and bind covalently to discrete proteins in mouse Liver. The data also suggest that one of the protein targets is cytochrome P450 2E1. Further studies will be necessary to elucidate the relationship between covalent binding of trichloroethylene and trichloroethylene toxicity.
• [EN] RAPAFUCIN DERIVATIVE COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS DÉRIVÉS DE LA RAPAFUCINE ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2021067439A1

  公开（公告）日：2021-04-08

  The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.