Boc-His-Trp-His-OMe | 1415241-39-2

• 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: Boc-His-Trp-His-OMe
• 英文别名: Boc-L-His-L-Trp-L-His-OMe；methyl (2S)-3-(1H-imidazol-5-yl)-2-[[(2S)-2-[[(2S)-3-(1H-imidazol-5-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoate
• CAS: 1415241-39-2
• 化学式: C₂₉H₃₆N₈O₆
• 分子量: 592.655
• InChiKey: ZTTWEZJTMRBCJF-HJOGWXRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  43
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  196
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Boc-His-Trp-His-OMe 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 0.25h， 以98%的产率得到His-Trp-His-OMe
  参考文献：
  名称：

  基于膜活性短合成肽的两亲物的抗真菌评价和机理研究

  摘要：

  对新型肽类抗生素的探索将这项研究导向设计和合成具有修饰的两亲性组氨酸和疏水色氨酸残基的短序列。二肽 Trp-His(1-Bn)-OMe/NHBn 和三肽 His(1-Bn)-Trp-His(1-Bn)-OMe/NHBn 的新结构类别显示出有前景的抗真菌和抗菌活性和膜溶解作用。二肽 Trp-His[1-(3,5-二叔丁基苄基)]-NHBn ( 13d ) 显示了理想的亲水-亲油平衡，它产生了最有希望的抗真菌活性，IC 50值为 2.10 μg/ mL 和 MIC = 3.81 μg/mL，对C. neoformans和对E. faecalis的抗菌活性和金黄色葡萄球菌具有相同的 IC 50值为 4.40 μg/mL 和 8.0 μg/mL 的 MIC。肽13d在MIC值及以上没有表现出细胞毒性和溶血作用。这种典型的两亲性进一步得到了机理解释的证实，这表明肽通过利用电荷和疏水性作为主要特征工具

  DOI：

  10.1016/j.bioorg.2022.106002
• 作为产物：
  描述：

  N-Boc-L-组氨酸 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 15.25h， 生成 Boc-His-Trp-His-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

• Synthetic amino acids‐based short amphipathic peptides exhibit antifungal activity by targeting cell membrane disruption
  作者：Shams Aaghaz、Komal Sharma、Indresh K. Maurya、Shivaprakash M. Rudramurthy、Shreya Singh、Vinod Kumar、Kulbhushan Tikoo、Rahul Jain

  DOI：10.1002/ddr.22041

  日期：——

  Boc-His-Trp-His[1-(4-tert-butylphenyl)] (10g) as the most promising inhibitor exhibiting IC50 value of 4.4 µg/mL against Cryptococcus neoformans. Analog 10g exhibit high selectivity to fungal cells and was nonhemolytic and noncytotoxic at its minimum inhibitory concentration. 10g produced fungicidal effect on growing cryptococcal cells and displayed synergistic effect with amphotericin B. Overall cationic character of

  有限数量的抗真菌药物的可用性产生了开发具有不同作用模式的新抗真菌药物的必要性。对一系列新肽的研究使我们确定 Boc-His-Trp-His[1-(4-叔丁基苯基)] ( 10g ) 是最有前途的抑制剂，其对新型隐球菌的 IC 50值为 4.4 µg/mL 。Analog 10g对真菌细胞表现出高选择性，并且在其最低抑制浓度下是非溶血性和非细胞毒性的。10g对生长的隐球菌细胞产生杀真菌作用，并与两性霉素B显示出协同作用。10g的整体阳离子特性导致与带负电荷的真菌膜相互作用，而疏水性增强了隐球菌细胞内的渗透，导致孔形成和膜破裂，如扫描电子显微镜、透射电子显微镜和共聚焦激光扫描显微镜分析所证明的那样。流式细胞术调查显示真菌细胞通过凋亡途径快速死亡。
• 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.
• Synthetic amino acids-derived peptides target Cryptococcus neoformans by inducing cell membrane disruption
  作者：Komal Sharma、Shams Aaghaz、Indresh Kumar Maurya、Krishna K. Sharma、Shreya Singh、Shivaprakash M. Rudramurthy、Vinod Kumar、Kulbhushan Tikoo、Rahul Jain

  DOI：10.1016/j.bioorg.2022.106252

  日期：2023.1
• 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.
• Antifungal evaluation and mechanistic investigations of membrane active short synthetic peptides-based amphiphiles
  作者：Komal Sharma、Shams Aaghaz、Indresh K. Maurya、Shivaprakash M. Rudramurthy、Shreya Singh、Vinod Kumar、Kulbhushan Tikoo、Rahul Jain

  DOI：10.1016/j.bioorg.2022.106002

  日期：2022.10

  The quest for new class of peptide-based antibiotics has steered this research towards the design and synthesis of short sequences possessing modified amphiphilic histidine along with hydrophobic tryptophan residues. The new structural class of dipeptides Trp-His(1-Bn)-OMe/NHBn and tripeptides His(1-Bn)-Trp-His(1-Bn)-OMe/NHBn demonstrated promising antifungal and antibacterial activities with membrane

  对新型肽类抗生素的探索将这项研究导向设计和合成具有修饰的两亲性组氨酸和疏水色氨酸残基的短序列。二肽 Trp-His(1-Bn)-OMe/NHBn 和三肽 His(1-Bn)-Trp-His(1-Bn)-OMe/NHBn 的新结构类别显示出有前景的抗真菌和抗菌活性和膜溶解作用。二肽 Trp-His[1-(3,5-二叔丁基苄基)]-NHBn ( 13d ) 显示了理想的亲水-亲油平衡，它产生了最有希望的抗真菌活性，IC 50值为 2.10 μg/ mL 和 MIC = 3.81 μg/mL，对C. neoformans和对E. faecalis的抗菌活性和金黄色葡萄球菌具有相同的 IC 50值为 4.40 μg/mL 和 8.0 μg/mL 的 MIC。肽13d在MIC值及以上没有表现出细胞毒性和溶血作用。这种典型的两亲性进一步得到了机理解释的证实，这表明肽通过利用电荷和疏水性作为主要特征工具