2-isopropyl-L-histidine | 479412-57-2

• 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-isopropyl-L-histidine
• 英文别名: (2S)-2-amino-3-(2-propan-2-yl-1H-imidazol-5-yl)propanoic acid
• CAS: 479412-57-2
• 化学式: C₉H₁₅N₃O₂
• 分子量: 197.237
• InChiKey: MXVDMXSWHBVPEL-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  92
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-isopropyl-L-histidine 在 盐酸 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 为溶剂， 4.0~60.0 ℃ 、275.8 kPa 条件下， 反应 3.5h， 生成 His(isopropyl)-Trp-His(isopropyl)-OMe
  参考文献：
  名称：

  Synthetically modified l-histidine-rich peptidomimetics exhibit potent activity against Cryptococcus neoformans

  摘要：

  We describe the synthesis and antimicrobial evaluation of structurally new peptidomimetics, rich in synthetically modified L-histidine. Two series of tripeptidomimetics were synthesized by varying lipophilicity at the C-2 position of L-histidine and at the N- and C-terminus. The data indicates that peptides (5f, 6f, 9f and 101) possessing highly lipophilic adamantan-1-yl group displayed strong inhibition of Cryptococcus neoformans. Peptide 6f is the most potent of all with IC50 and MFC values of 0.60 and 0.63 mu g/mL, respectively, compared to the commercial drug amphotericin B (IC50 = 0.69 and MFC = 1.25 mu g/mL). The selectivity of these peptides to microbial pathogen was examined by a tryptophan fluorescence quenching study and transmission electron microscopy. These studies indicate that the peptides plausibly interact with the mimic membrane of pathogen by direct insertion, and results in disruption of membrane of pathogen. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.120
• 作为产物：
  描述：

  N-α-trifluoroacetyl-L-histidine methyl ester 在 盐酸 、 ammonium peroxydisulfate 、 Dowex ion-exchange resin 、 硫酸 、 silver nitrate 作用下， 反应 0.25h， 生成 2-isopropyl-L-histidine
  参考文献：
  名称：

  促甲状腺激素释放激素（TRH）类似物，对TRH受体亚型2具有选择性。

  摘要：

  合成了促甲状腺激素释放激素（TRH）类似物，其中位于中心的组氨酸残基的咪唑环的C-2位置被各种烷基取代，并被研究用作TRH受体亚型1（TRH-R1）和亚型2的激动剂（TRH-R2）。发现几种类似物是TRH-R2的选择性激动剂，其不显示TRH-R1的活化。例如，发现类似物4（R = c-C3H5）以0.41 microM的效力（EC50）激活TRH-R2，但没有激活TRH-R1（效力> 100 microM）。这项研究描述了TRH-R2特异性激动剂的首次发现，并为设计以CNS有效的TRH肽提供了动力。

  DOI：

  10.1021/jm0505462

文献信息

• Synthetically modified l-histidine-rich peptidomimetics exhibit potent activity against Cryptococcus neoformans
  作者：Amit Mahindra、Nitin Bagra、Nishima Wangoo、Rohan Jain、Shabana I. Khan、Melissa R. Jacob、Rahul Jain

  DOI：10.1016/j.bmcl.2014.04.120

  日期：2014.7

  We describe the synthesis and antimicrobial evaluation of structurally new peptidomimetics, rich in synthetically modified L-histidine. Two series of tripeptidomimetics were synthesized by varying lipophilicity at the C-2 position of L-histidine and at the N- and C-terminus. The data indicates that peptides (5f, 6f, 9f and 101) possessing highly lipophilic adamantan-1-yl group displayed strong inhibition of Cryptococcus neoformans. Peptide 6f is the most potent of all with IC50 and MFC values of 0.60 and 0.63 mu g/mL, respectively, compared to the commercial drug amphotericin B (IC50 = 0.69 and MFC = 1.25 mu g/mL). The selectivity of these peptides to microbial pathogen was examined by a tryptophan fluorescence quenching study and transmission electron microscopy. These studies indicate that the peptides plausibly interact with the mimic membrane of pathogen by direct insertion, and results in disruption of membrane of pathogen. (C) 2014 Elsevier Ltd. All rights reserved.
• Thyrotropin-Releasing Hormone (TRH) Analogues That Exhibit Selectivity to TRH Receptor Subtype 2
  作者：Navneet Kaur、Xinping Lu、Marvin C. Gershengorn、Rahul Jain

  DOI：10.1021/jm0505462

  日期：2005.9.1

  Thyrotropin-releasing hormone (TRH) analogues in which the C-2 position of the imidazole ring of the centrally placed histidine residue is substituted with various alkyl groups were synthesized and studied as agonists for TRH receptor subtype 1 (TRH-R1) and subtype 2 (TRH-R2). Several analogues were found to be selective agonists for TRH-R2 exhibiting no activation of TRH-R1. For example, analogue

  合成了促甲状腺激素释放激素（TRH）类似物，其中位于中心的组氨酸残基的咪唑环的C-2位置被各种烷基取代，并被研究用作TRH受体亚型1（TRH-R1）和亚型2的激动剂（TRH-R2）。发现几种类似物是TRH-R2的选择性激动剂，其不显示TRH-R1的活化。例如，发现类似物4（R = c-C3H5）以0.41 microM的效力（EC50）激活TRH-R2，但没有激活TRH-R1（效力> 100 microM）。这项研究描述了TRH-R2特异性激动剂的首次发现，并为设计以CNS有效的TRH肽提供了动力。