Boc-Trp-His-NHBzl | 1184962-81-9

• 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-Trp-His-NHBzl
• 英文别名: Boc-Trp-His-NHBn；tert-butyl N-[(2S)-1-[[(2S)-1-(benzylamino)-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate
• CAS: 1184962-81-9
• 化学式: C₂₉H₃₄N₆O₄
• 分子量: 530.627
• InChiKey: CSXUWPFDACHWNE-DQEYMECFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  141
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-Trp-His-NHBzl 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.28h， 生成 His-Trp-His-NHBzl
  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'-二异丙基碳二亚胺 作用下， 以 水 为溶剂， 20.0~60.0 ℃ 、275.8 kPa 条件下， 反应 0.75h， 生成 Boc-Trp-His-NHBzl
  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

• 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。
• 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.
• Discovery of Trp-His and His-Arg Analogues as New Structural Classes of Short Antimicrobial Peptides
  作者：Rohit K. Sharma、Ravi P. Reddy、Werner Tegge、Rahul Jain

  DOI：10.1021/jm900622d

  日期：2009.12.10

  Naturally occurring antimicrobial peptides contain a large number of amino acid residues, which limits their clinical applicability. In search of short antimicrobial peptides, which represent a possible alternative for lead structures to fight antibiotic resistant microbial infections, a series of synthetic peptide analogues based oil Trp-His and His-Arg structural frameworks have been prepared and found to be active against several Gram-negative and Gram-positive bacterial strains as well as against a fungal strain with MIC values of the most potent Structures in the range of 5-20 mu g/mL ((IC50 in the range of 1-5 mu g/mL). The synthesized peptides showed no cytotoxic effect in an MTT assay up to the highest test concentration of 200 mu g/mL. A combination of small size, presence of unnatural amino acids, high antimicrobial activity, and absence of cytotoxicity reveals the synthesized Trp-His and His-Arg analogues as promising candidates for novel antimicrobial therapeutics.
• 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
• 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.