N(α)-[(9H-fluoren-9-ylmethoxy)carbonyl]-N(π)-(8-phenyloctyl)-L-histidine methyl ester | 1334648-27-9

• 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: N(α)-[(9H-fluoren-9-ylmethoxy)carbonyl]-N(π)-(8-phenyloctyl)-L-histidine methyl ester
• 英文别名: N(α)-[(9H-fluoren-9-ylmethoxy)carbonyl]-N(ϖ)-(8-phenyloctyl)-L-histidine methyl ester；methyl (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[3-(8-phenyloctyl)imidazol-4-yl]propanoate
• CAS: 1334648-27-9
• 化学式: C₃₆H₄₁N₃O₄
• 分子量: 579.739
• InChiKey: AOAKOMOGWDSFCR-UMSFTDKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  43
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  82.4
• 氢给体数：
  1
• 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 methyl ester 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.0h， 以64%的产率得到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
• 作为产物：
  描述：

  N-Fmoc-N'-三苯甲基-L-组氨酸 在 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 、 二氯甲烷 为溶剂， 反应 34.5h， 生成 N(α)-[(9H-fluoren-9-ylmethoxy)carbonyl]-N(π)-(8-phenyloctyl)-L-histidine methyl ester
  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

• 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.