Trp-His(phenyl)-OMe | 1613201-84-5

• 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: Trp-His(phenyl)-OMe
• 英文别名: methyl (2S)-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-3-(2-phenyl-1H-imidazol-5-yl)propanoate
• CAS: 1613201-84-5
• 化学式: C₂₄H₂₅N₅O₃
• 分子量: 431.494
• InChiKey: VRUCZIPKMWQQCZ-FPOVZHCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 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-phenyl-L-histidine 、 Trp-His(phenyl)-OMe 在 endo-N-Hydroxy-5-norbornene-2,3-dicarboximide 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 Boc-His(2-phenyl)-Trp-His(2-phenyl)-OMe
  参考文献：
  名称：

  Discovery of a Membrane-Active, Ring-Modified Histidine Containing Ultrashort Amphiphilic Peptide That Exhibits Potent Inhibition of Cryptococcus neoformans

  摘要：

  The new structural classes of ultrashort peptides that exhibit potent microbicidal action have potential as future drugs. Herein, we report that C-2 arylated histidines containing tripeptides His(2-Ar)-Trp-His(2-Ar) exhibit potent antifungal activity against Cryptococcus neoformans with high selectivity. The most potent peptide 12f [His(2-biphenyl)-Trp-His(2-biphenyl)] displayed high in vitro activity against C. neoformans (IC50 = 0.35 mu g/mL, MIC = MFC = 0.63 mu g/mL) with a selectivity index of >28 and 2 times higher potency compared to amphotericin B. Peptide 12f exhibited proteolytic stability, with no apparent hemolytic activity. The mechanism of action study of 12f by confocal laser scanning microscopy and electron microscopy indicates nuclear fragmentation and membrane disruption of C. neoformans cells. Combinations of 12f with fluconazole and amphotericin B at subinhibitory concentration were synergistic against C. neoformans. This study suggests that 12f is a new structural class of amphiphilic peptide with rapid fungicidal activity caused by C. neoformans.

  DOI：

  10.1021/acs.jmedchem.7b00481
• 作为产物：
  描述：

  N-α-Boc-2-phenyl-L-histidine 在 盐酸 、 endo-N-Hydroxy-5-norbornene-2,3-dicarboximide 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.75h， 生成 Trp-His(phenyl)-OMe
  参考文献：
  名称：

  Discovery of a Membrane-Active, Ring-Modified Histidine Containing Ultrashort Amphiphilic Peptide That Exhibits Potent Inhibition of Cryptococcus neoformans

  摘要：

  The new structural classes of ultrashort peptides that exhibit potent microbicidal action have potential as future drugs. Herein, we report that C-2 arylated histidines containing tripeptides His(2-Ar)-Trp-His(2-Ar) exhibit potent antifungal activity against Cryptococcus neoformans with high selectivity. The most potent peptide 12f [His(2-biphenyl)-Trp-His(2-biphenyl)] displayed high in vitro activity against C. neoformans (IC50 = 0.35 mu g/mL, MIC = MFC = 0.63 mu g/mL) with a selectivity index of >28 and 2 times higher potency compared to amphotericin B. Peptide 12f exhibited proteolytic stability, with no apparent hemolytic activity. The mechanism of action study of 12f by confocal laser scanning microscopy and electron microscopy indicates nuclear fragmentation and membrane disruption of C. neoformans cells. Combinations of 12f with fluconazole and amphotericin B at subinhibitory concentration were synergistic against C. neoformans. This study suggests that 12f is a new structural class of amphiphilic peptide with rapid fungicidal activity caused by C. neoformans.

  DOI：

  10.1021/acs.jmedchem.7b00481

文献信息

• Synthesis and antimicrobial activities of His(2-aryl)-Arg and Trp-His(2-aryl) classes of dipeptidomimetics
  作者：Amit Mahindra、Krishna K. Sharma、Dinesh Rathore、Shabana. I. Khan、Melissa R. Jacob、Rahul Jain

  DOI：10.1039/c4md00041b

  日期：——

  In this communication, we report the design, synthesis andin vitroantimicrobial activity of ultra short peptidomimetics.

  在这份通讯中，我们报告了超短肽类模拟物的设计、合成和体外抗菌活性。
• Anticryptococcal activity and mechanistic studies of short amphipathic peptides
  作者：Shams Aaghaz、Komal Sharma、Indresh K. Maurya、Shivaprakash M. Rudramurthy、Shreya Singh、Vinod Kumar、Kulbhushan Tikoo、Rahul Jain

  DOI：10.1002/ardp.202200576

  日期：——

  L-histidines-containing peptides are synthesized that exhibit promising activity against C. neoformans. Analog 11d [L-His(2-adamantyl)-L-Trp-L-His(2-phenyl)-OMe] produced potency with an IC50 of 3.02 µg/ml (MIC = 5.49 µg/ml). This peptide is noncytotoxic and nonhaemolytic at the MIC and displays synergistic effects with amphotericin B at subinhibitory concentration. Mechanistic investigation of 11d using

  新型隐球菌是一种机会性真菌病原体，可在免疫功能低下的人中引起隐球菌病。合成了一系列修饰的含有 L-组氨酸的肽，这些肽对新型隐球菌表现出有前途的活性。类似物11d [L-His(2-adamantyl)-L-Trp-L-His(2-phenyl)-OMe] 产生效力，IC 50为 3.02 µg/ml（MIC = 5.49 µg/ml）。该肽在 MIC 下无细胞毒性和非溶血性，在亚抑制浓度下与两性霉素 B 显示出协同作用。使用显微工具对11d的机理研究表明C. neoformans的细胞壁和膜破坏，而流式细胞术分析证实细胞凋亡导致的细胞死亡。该研究表明11d具有抗真菌潜力，并通过快速起效发挥作用。
• Discovery of a Membrane-Active, Ring-Modified Histidine Containing Ultrashort Amphiphilic Peptide That Exhibits Potent Inhibition of <i>Cryptococcus neoformans</i>
  作者：Krishna K. Sharma、Indresh Kumar Maurya、Shabana I. Khan、Melissa R. Jacob、Vinod Kumar、Kulbhushan Tikoo、Rahul Jain

  DOI：10.1021/acs.jmedchem.7b00481

  日期：2017.8.10

  The new structural classes of ultrashort peptides that exhibit potent microbicidal action have potential as future drugs. Herein, we report that C-2 arylated histidines containing tripeptides His(2-Ar)-Trp-His(2-Ar) exhibit potent antifungal activity against Cryptococcus neoformans with high selectivity. The most potent peptide 12f [His(2-biphenyl)-Trp-His(2-biphenyl)] displayed high in vitro activity against C. neoformans (IC50 = 0.35 mu g/mL, MIC = MFC = 0.63 mu g/mL) with a selectivity index of >28 and 2 times higher potency compared to amphotericin B. Peptide 12f exhibited proteolytic stability, with no apparent hemolytic activity. The mechanism of action study of 12f by confocal laser scanning microscopy and electron microscopy indicates nuclear fragmentation and membrane disruption of C. neoformans cells. Combinations of 12f with fluconazole and amphotericin B at subinhibitory concentration were synergistic against C. neoformans. This study suggests that 12f is a new structural class of amphiphilic peptide with rapid fungicidal activity caused by C. neoformans.