色氨酸EP杂质A | 132685-02-0

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 色氨酸EP杂质A
• 中文别名: 色氨酸相关物质A；粉色E
• 英文名称: 1,1'-ethylidenebis(L-tryptophan)
• 英文别名: 1,1'-Ethylidenebis[l-tryptophan]；(2S)-2-amino-3-[1-[1-[3-[(2S)-2-amino-2-carboxyethyl]indol-1-yl]ethyl]indol-3-yl]propanoic acid
• CAS: 132685-02-0
• 化学式: C₂₄H₂₆N₄O₄
• 分子量: 434.495
• InChiKey: DETVQFQGSVEQBH-PMACEKPBSA-N

物化性质

• 熔点：
  >210°C (dec.)
• 沸点：
  718.5±60.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于水基（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  137
• 氢给体数：
  4
• 氢受体数：
  6

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  2,4-二硝基氟苯 、 色氨酸EP杂质A 在 碳酸氢钠 作用下， 以 水 、 乙腈 为溶剂， 反应 3.0h， 以50%的产率得到1,1'-Ethylidenebis(N-2,4-dinitrophenyl-L-tryptophan)
  参考文献：
  名称：

  1,1′-ethylidenebis(L-tryptophan), structure determination of contaminant “97” - implicated in the Eosinophilia-myalgia syndrome (EMS)

  摘要：

  The condensation of tryptophan and acetaldehyde affords a bisindolylaminal of tryptophan which is indistinguishable from contaminant "97". The formation and decomposition of aminals is addressed in light of epidemiological evidence linking them to a recent outbreak of EMS.

  DOI：

  10.1016/s0040-4039(00)74469-8
• 作为产物：
  描述：

  乙醛 、 L-色氨酸 在 盐酸 作用下， 以 水 为溶剂， 反应 0.33h， 以30%的产率得到粉色E
  参考文献：
  名称：

  1,1′-ethylidenebis(L-tryptophan), structure determination of contaminant “97” - implicated in the Eosinophilia-myalgia syndrome (EMS)

  摘要：

  The condensation of tryptophan and acetaldehyde affords a bisindolylaminal of tryptophan which is indistinguishable from contaminant "97". The formation and decomposition of aminals is addressed in light of epidemiological evidence linking them to a recent outbreak of EMS.

  DOI：

  10.1016/s0040-4039(00)74469-8

文献信息

• Regulation of T cell-mediated immunity by tryptophan
  申请人：Medical College of Georgia Research Institute, Inc.

  公开号：US20010001040A1

  公开（公告）日：2001-05-10

  A mechanism of macrophage-induced T cell suppression is the selective elimination of tryptophan and/or increase in one or more tryptophan metabolites within the local macrophage microenvironment Studies demonstrate that expression of IDO can serve as a marker of suppression of T cell activation, and may play a significant role in allogeneic pregnancy and therefore other types of transplantation, and that inhibitors of IDO can be used to activate T cells and therefore enhance T cell activation when the T cells are suppressed by pregnancy, malignancy or a virus such as HIV. Inhibiting tryptophan degradation (and thereby increasing tryptophan concentration while decreasing tryptophan metabolite concentration), or supplementing tryptophan concentration, can therefore be used in addition to, or in place of, inhibitors of IDO. Similarly, increasing tryptophan degradation (thereby, decreasing tryptophan concentration and increasing tryptophan metabolite concentration), for example, by increasing IDO concentration or IDO activity, can suppress T cells. Although described particularly with reference to IDO regulation, one can instead manipulate local tryptophan concentrations, and/or modulate the activity of the high affinity tryptophan transporter, and/or administer other tryptophan degrading enzymes. Regulation can be further manipulated using cytokines such as macrophage colony stimulating factor, interferon gamma, alone or in combination with antigen or other cytokines.

  巨噬细胞诱导 T 细胞抑制的机制之一是色氨酸的选择性消除和/或局部巨噬细胞微环境中一种或多种色氨酸代谢物的增加 研究表明，IDO 的表达可作为抑制 T 细胞活化的标志物，并可能在异体妊娠和其他类型的移植中发挥重要作用；当 T 细胞因妊娠、恶性肿瘤或 HIV 等病毒而受到抑制时，IDO 抑制剂可用于激活 T 细胞，从而增强 T 细胞的活化。因此，抑制色氨酸降解（从而增加色氨酸浓度，同时降低色氨酸代谢物浓度）或补充色氨酸浓度，可作为 IDO 抑制剂的补充或替代物。同样，增加色氨酸降解（从而降低色氨酸浓度并增加色氨酸代谢物浓度），例如通过增加 IDO 浓度或 IDO 活性，可以抑制 T 细胞。虽然特别提到了 IDO 的调节，但人们也可以操纵局部色氨酸的浓度，和/或调节高亲和性色氨酸转运体的活性，和/或管理其他色氨酸降解酶。还可以使用细胞因子，如巨噬细胞集落刺激因子、γ干扰素，单独或与抗原或其他细胞因子结合使用，进一步进行调节。
• Kinetics of the Formation and Decomposition of 1,1‘-Ethylidenebis[<scp>l</scp>-tryptophan], an Eosinophilia Myalgia Syndrome-Associated Compound
  作者：Tong-Jen Fu

  DOI：10.1021/jf950421d

  日期：1996.1.1

  1, 1'-Ethylidenebis[L-tryptophan] (EBT), an impurity found in L-tryptophan associated with eosinophilia myalgia syndrome (EMS), has been suggested as one of the causative agents for EMS. Highperformance liquid chromatography was used to study the kinetics of EBT formation and decomposition in buffer systems. Initial EBT decomposition was first-order with respect to EBT and strongly pH-dependent. The pH profile suggested that decomposition involved the addition of one proton. The value of the critical pH, above which the rate of EBT decomposition remained constant, was determined to be 4.8. The rate of EBT decomposition increased with increasing temperature, and the activation energy was calculated to be 12.5 kcal/mol. The rate of EBT formation decreased with increasing pH and decreasing temperature. The presence of excess acetaldehyde increased EBT formation to a lesser extent than did the presence of excess L-tryptophan. The results of this study are consistent with the hypothesis that EBT was formed during the absorption stage of the cation exchange operation in the commercial process that resulted in the formation of EMS-associated L-tryptophan.
• REGULATION OF T CELL-MEDIATED IMMUNITY BY TRYPTOPHAN
  申请人：MUNN David

  公开号：US20120288472A1

  公开（公告）日：2012-11-15

  A mechanism of macrophage-induced T cell suppression is the selective elimination of tryptophan and/or increase in one or more tryptophan metabolites within the local macrophage microenvironment Expression of IDO can serve as a marker of suppression of T cell activation, and may play a significant role in allogeneic pregnancy and other types of transplantation. Inhibitors of IDO can be used to activate T cells. Inhibiting tryptophan degradation, or supplementing tryptophan concentration, can be used in addition to, or in place of, inhibitors of IDO. Increasing tryptophan degradation (thereby, decreasing tryptophan concentration and increasing tryptophan metabolite concentration), for example, by increasing IDO concentration or IDO activity, can suppress T cells. One can manipulate local tryptophan concentrations, and/or modulate the activity of the high affinity tryptophan transporter, and/or administer tryptophan degrading enzymes. Regulation can be further manipulated using cytokines such as MCSF, IFNγ, alone or in combination with antigen or other cytokines.
• US6451840B1
  申请人：——

  公开号：US6451840B1

  公开（公告）日：2002-09-17
• US6482416B2
  申请人：——

  公开号：US6482416B2

  公开（公告）日：2002-11-19