N(α)-[(9H-fluoren-9-ylmethoxy)carbonyl]-N(π)-(8-phenyloctyl)-L-histidine | 1334648-24-6

• 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: N(α)-[(9H-fluoren-9-ylmethoxy)carbonyl]-N(π)-(8-phenyloctyl)-L-histidine
• 英文别名: Fmoc-His(N^π-(CH2)₈Ph)-OH；N(α)-[(9H-fluoren-9-ylmethoxy)carbonyl]-N(ϖ)-(8-phenyloctyl)-L-histidine；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[3-(8-phenyloctyl)imidazol-4-yl]propanoic acid
• CAS: 1334648-24-6
• 化学式: C₃₅H₃₉N₃O₄
• 分子量: 565.712
• InChiKey: IRRVUWANVQODOX-XIFFEERXSA-N

物化性质

• 沸点：
  799.6±60.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  42
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  93.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N(α)-[(9H-fluoren-9-ylmethoxy)carbonyl]-N(π)-(8-phenyloctyl)-L-histidine 、 烯丙醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 3.75h， 以80%的产率得到
  参考文献：
  名称：

  Mitsunobu的恶作剧：邻居定向的组氨酸N（τ）-烷基化作用提供了对含有选择性功能化的咪唑鎓杂环的肽的访问权†

  摘要：

  几乎没有方法可产生含有带有选择性N（τ），N（π）-双烷基化咪唑环的His残基的肽。我们已经发现，在某些条件下，醇与具有N（π）-烷基化His残基的肽的树脂上的Mitsunobu偶联导致咪唑N（τ）氮的选择性和高产率烷基化。该反应需要存在近端的磷酸，羧酸或磺酸，并通过涉及光延中间体的明显的分子内机理进行。这些转化特别适用于磷酸肽，其中现在有可能通过阳离子组氨酸咪唑鎓离子对一个磷酰基阴离子电荷进行“电荷掩蔽”。这种化学作用使人们可以选择性地获得含有差异化功能的咪唑鎓杂环的肽，

  DOI：

  10.1039/c5ob00171d
• 作为产物：
  描述：

  N-Fmoc-N'-三苯甲基-L-组氨酸 在 盐酸 、 三异丙基硅烷 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 37.5h， 生成 N(α)-[(9H-fluoren-9-ylmethoxy)carbonyl]-N(π)-(8-phenyloctyl)-L-histidine
  参考文献：
  名称：

  Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1

  摘要：

  The polo-box domain (PBD) of polo-like kinase 1 (Plk1) is essentially required for the function of Plk1 in cell proliferation. The availability of the phosphopeptide-binding pocket on PBD provides a unique opportunity to develop novel protein-protein interaction inhibitors. Recent identification of a minimal 5-residue-long phosphopeptide, PLHSpT, as a Plk1 PBD-specific ligand has led to the development of several peptide-based inhibitors, but none of them is cyclic peptide. Through the combination of single-peptoid mimics and thio-ether bridged cyclization, we successfully demonstrated for the first time two cyclic peptomers, PL-116 and PL-120, dramatically improved the binding affinity without losing mono-specificity against Plk1 PBD in comparison with the linear parental peptide, PLHSpT. These cyclic peptomers could serve as promising templates for future drug designs to inhibit Plk1 PBD. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.020

文献信息

• Peptide mimetic ligands of polo-like kinase 1 polo box domain and methods of use
  申请人：Burke, Jr. Terrence R.

  公开号：US10266565B2

  公开（公告）日：2019-04-23

  Novel compounds are provided that bind to polo-like kinases through the polo-box domain. In certain embodiments, the novel compounds are PEGylated peptides. The PEGylated peptides in accordance with the invention demonstrate high PBD-binding affinity. In certain embodiments, the PEGylated peptides have also achieved activities in whole cell systems. The invention also provides compounds that bind polo-like kinases through the polo-box domain and possess reduced anionic charge. Further provided are methods of design and/or synthesis of the PEGylated peptides and methods of use thereof. The invention provides methods of use of the compounds and methods of synthesis of the compounds.

  提供了一种新型化合物，通过波洛盒结构结合波洛样激酶。在某些实施例中，这些新型化合物是PEG化肽。根据本发明，这些PEG化肽表现出高PBD结合亲和力。在某些实施例中，这些PEG化肽在整个细胞系统中也表现出活性。本发明还提供了一种通过波洛盒结构结合波洛样激酶且具有降低阴离子电荷的化合物。此外，还提供了PEG化肽的设计和/或合成方法以及使用这些方法。本发明提供了这些化合物的使用方法和合成方法。
• Investigation of Unanticipated Alkylation at the N(π) Position of a Histidyl Residue Under Mitsunobu Conditions and Synthesis of Orthogonally Protected Histidine Analogues
  作者：Wenjian Qian、Fa Liu、Terrence R. Burke

  DOI：10.1021/jo201599c

  日期：2011.11.4

  We had previously reported that Mitsunobu-based introduction of alkyl substituents onto the imidazole N(pi)-position of a key histidine residue in phosphothreonine-containing peptides can impart high binding affinity against the polo-box domain of polo-like kinase 1. Our current paper investigates the mechanism leading to this N(pi)-alkylation and provides synthetic methodologies that permit the facile synthesis of histidine N(pi)-modified peptides. These agents represent new and potentially important tools for biological studies.
• Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1
  作者：Ravichandran N. Murugan、Jung-Eun Park、Dan Lim、Mija Ahn、Chaejoon Cheong、Taeho Kwon、Ky-Youb Nam、Sun Ho Choi、Bo Yeon Kim、Do-Young Yoon、Michael B. Yaffe、Dae-Yeul Yu、Kyung S. Lee、Jeong Kyu Bang

  DOI：10.1016/j.bmc.2013.02.020

  日期：2013.5

  The polo-box domain (PBD) of polo-like kinase 1 (Plk1) is essentially required for the function of Plk1 in cell proliferation. The availability of the phosphopeptide-binding pocket on PBD provides a unique opportunity to develop novel protein-protein interaction inhibitors. Recent identification of a minimal 5-residue-long phosphopeptide, PLHSpT, as a Plk1 PBD-specific ligand has led to the development of several peptide-based inhibitors, but none of them is cyclic peptide. Through the combination of single-peptoid mimics and thio-ether bridged cyclization, we successfully demonstrated for the first time two cyclic peptomers, PL-116 and PL-120, dramatically improved the binding affinity without losing mono-specificity against Plk1 PBD in comparison with the linear parental peptide, PLHSpT. These cyclic peptomers could serve as promising templates for future drug designs to inhibit Plk1 PBD. (C) 2013 Elsevier Ltd. All rights reserved.
• Mitsunobu mischief: neighbor-directed histidine N(τ)-alkylation provides access to peptides containing selectively functionalized imidazolium heterocycles
  作者：Wen-Jian Qian、Terrence R. Burke

  DOI：10.1039/c5ob00171d

  日期：——

  few methodologies that yield peptides containing His residues with selective N(τ), N(π)-bis-alkylated imidazole rings. We have found that, under certain conditions, on-resin Mitsunobu coupling of alcohols with peptides having a N(π)-alkylated His residue results in selective and high-yield alkylation of the imidazole N(τ) nitrogen. The reaction requires the presence of a proximal phosphoric, carboxylic

  几乎没有方法可产生含有带有选择性N（τ），N（π）-双烷基化咪唑环的His残基的肽。我们已经发现，在某些条件下，醇与具有N（π）-烷基化His残基的肽的树脂上的Mitsunobu偶联导致咪唑N（τ）氮的选择性和高产率烷基化。该反应需要存在近端的磷酸，羧酸或磺酸，并通过涉及光延中间体的明显的分子内机理进行。这些转化特别适用于磷酸肽，其中现在有可能通过阳离子组氨酸咪唑鎓离子对一个磷酰基阴离子电荷进行“电荷掩蔽”。这种化学作用使人们可以选择性地获得含有差异化功能的咪唑鎓杂环的肽，