L-Trp-L-His[2-(adamantan-1-yl)]-OMe | 1185192-49-7

• 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: L-Trp-L-His[2-(adamantan-1-yl)]-OMe
• 英文别名: methyl (2S)-3-[2-(1-adamantyl)-1H-imidazol-5-yl]-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]propanoate
• CAS: 1185192-49-7
• 化学式: C₂₈H₃₅N₅O₃
• 分子量: 489.618
• InChiKey: HTOLJQIDFJLXEC-YBPWQOLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-α-Boc-2-(adamantan-1-yl)-L-histidine 、 L-Trp-L-His[2-(adamantan-1-yl)]-OMe 在 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 水 为溶剂， 60.0 ℃ 、275.8 kPa 条件下， 反应 0.5h， 生成 Boc-His(adamantan-1-yl)-Trp-His(adamantan-1-yl)-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：

  2-adamantyl-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 2.75h， 生成 L-Trp-L-His[2-(adamantan-1-yl)]-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

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.