4-(3-methoxy-4-{[(9H-fluoren-9-ylmethoxycarbonyl)(prop-2-ynyl)-amino]methyl}phenoxy)butanoic acid | 1009362-00-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 4-(3-methoxy-4-{[(9H-fluoren-9-ylmethoxycarbonyl)(prop-2-ynyl)-amino]methyl}phenoxy)butanoic acid
• 英文别名: Fmoc-N-propargyl-MPBA；4-[4-[[9H-fluoren-9-ylmethoxycarbonyl(prop-2-ynyl)amino]methyl]-3-methoxyphenoxy]butanoic acid
• CAS: 1009362-00-8
• 化学式: C₃₀H₂₉NO₆
• 分子量: 499.563
• InChiKey: VYWLLSRJVDDCOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(3-methoxy-4-{[(9H-fluoren-9-ylmethoxycarbonyl)(prop-2-ynyl)-amino]methyl}phenoxy)butanoic acid 在 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 、 哌啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以51%的产率得到4-{3-甲氧基-4-[(丙-2-炔基氨基)甲基]苯氧基}丁酸
  参考文献：
  名称：

  用于合成含 1,4-三唑的环状四肽和五肽的骨架酰胺接头策略

  摘要：

  选择主链酰胺接头策略用于固相合成含三唑的环状四肽和五肽。衍生自 4-羟基-2-甲氧基苯甲醛的炔烃取代的接头通过使用标准的“基于 Fmoc”的固相化学延长并通过偶氮酸的偶联终止。在溶液中，肽通过 Cu-1 催化的叠氮化物-炔环加成反应环化。固体支持的合成线性肽必须在环化之前裂解。作为环状四肽的一个例子，环-[Pro-Val-Pro-Tyr] (2) 的三唑类似物是通过固相/溶液相方法制备的。对于环状五肽，选择 segetalin B (3) 作为模型化合物以显示该方法的适用性。

  DOI：

  10.1002/ejoc.200800143
• 作为产物：
  描述：

  D-果糖-1-磷酸钡盐 在 sodium cyanoborohydride 、 碳酸氢钠 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 乙腈 为溶剂， 反应 17.5h， 生成 4-(3-methoxy-4-{[(9H-fluoren-9-ylmethoxycarbonyl)(prop-2-ynyl)-amino]methyl}phenoxy)butanoic acid
  参考文献：
  名称：

  Biomimetic Screening of Class-B G Protein-Coupled Receptors

  摘要：

  The 41-amino acid peptide corticotropin releasing factor (CRF) is a major modulator of the mammalian stress response. Upon stressful stimuli, it binds to the corticotropin releasing factor receptor 1 (CRF1R), a typical member of the class-B G-protein-coupled receptors (GPCRs) and a prime target in the treatment of mood disorders. To chemically probe the molecular interaction of CRF with the transmembrane domain of its cognate receptor, we developed a high-throughput conjugation approach that mimics the natural activation mechanism of class-B GPCRs. An acetylene-tagged peptide library was synthesized and conjugated to an azide-modified high-affinity carrier peptide derived from the CRF C-terminus using copper-catalyzed dipolar cycloaddition. The resulting conjugates reconstituted potent agonists and were tested in situ for activation of the CRF1 receptor in a cell-based assay. By use of this approach we (i) defined the minimal sequence motif that is required for full receptor activation, (ii) identified the critical functional groups and structure activity relationships, (iii) developed an optimized, highly modified peptide probe with high potency (EC50 = 4 nM) that is specific for the activation domain of the receptor, and (iv) probed the behavioral role of CRF receptors in living mice. The membrane recruitment by a high-affinity carrier enhanced the potency of the tethered peptides by >4 orders of magnitude and thus allowed the testing of very weak initial fragments that otherwise would have been inactive on their own. As no chromatography purification of the test peptides was necessary, a substantial increase in screening throughput was achieved. Importantly, the peptide conjugates can be used to probe the endogenous receptor in its native environment in vivo.

  DOI：

  10.1021/ja200160s

文献信息

• SCREENING METHOD FOR GPCR LIGANDS
  申请人：Hausch Felix

  公开号：US20090286259A1

  公开（公告）日：2009-11-19

  This invention relates to a method of identifying a compound capable of binding to a target domain of a G-protein coupled receptor comprising the steps of: (a) providing a receptor comprising said target domain and a first group linked to said target domain; (b) bringing into contact said receptor of (a) with a test molecule comprising a second group and said compound linked to each other, wherein said first group binds said second group; and (c) determining, subsequent to the binding of said first group to said second group, whether said compound binds to said target domain.
• US8623606B2
  申请人：——

  公开号：US8623606B2

  公开（公告）日：2014-01-07
• [EN] SCREENING METHOD FOR GPCR LIGANDS<br/>[FR] PROCÉDÉ DE CRIBLAGE POUR LIGANDS GPCR
  申请人：MAX PLANCK GESELLSCHAFT

  公开号：WO2008022716A2

  公开（公告）日：2008-02-28

  [EN] This invention relates to a method of identifying a compound capable of binding to a target domain of a G-protein coupled receptor comprising the steps of: (a) providing a receptor comprising said target domain and a first group linked to said target domain; (b) bringing into contact said receptor of (a) with a test molecule comprising a second group and said compound linked to each other, wherein said first group binds said second group; and (c) determining, subsequent to the binding of said first group to said second group, whether said compound binds to said target domain.
  [FR] La présente invention concerne un procédé destiné à identifier un composé capable de se lier à un domaine cible d'un récepteur couplé à la protéine G, le procédé consistant à : (a) fournir un récepteur comprenant ledit domaine cible et un premier groupe lié au domaine cible; (b) mettre en contact le récepteur issu de (a) avec une molécule test comprenant un second groupe et ledit composé liés entre eux, le premier groupe se liant au second groupe; et (c) déterminer, après la liaison du premier groupe au second groupe, si le composé se lie au domaine cible.
• Biomimetic Screening of Class-B G Protein-Coupled Receptors
  作者：Christian Devigny、Francisco Perez-Balderas、Bastiaan Hoogeland、Serena Cuboni、Rudolf Wachtel、Christoph P. Mauch、Katharine J. Webb、Jan M. Deussing、Felix Hausch

  DOI：10.1021/ja200160s

  日期：2011.6.15

  The 41-amino acid peptide corticotropin releasing factor (CRF) is a major modulator of the mammalian stress response. Upon stressful stimuli, it binds to the corticotropin releasing factor receptor 1 (CRF1R), a typical member of the class-B G-protein-coupled receptors (GPCRs) and a prime target in the treatment of mood disorders. To chemically probe the molecular interaction of CRF with the transmembrane domain of its cognate receptor, we developed a high-throughput conjugation approach that mimics the natural activation mechanism of class-B GPCRs. An acetylene-tagged peptide library was synthesized and conjugated to an azide-modified high-affinity carrier peptide derived from the CRF C-terminus using copper-catalyzed dipolar cycloaddition. The resulting conjugates reconstituted potent agonists and were tested in situ for activation of the CRF1 receptor in a cell-based assay. By use of this approach we (i) defined the minimal sequence motif that is required for full receptor activation, (ii) identified the critical functional groups and structure activity relationships, (iii) developed an optimized, highly modified peptide probe with high potency (EC50 = 4 nM) that is specific for the activation domain of the receptor, and (iv) probed the behavioral role of CRF receptors in living mice. The membrane recruitment by a high-affinity carrier enhanced the potency of the tethered peptides by >4 orders of magnitude and thus allowed the testing of very weak initial fragments that otherwise would have been inactive on their own. As no chromatography purification of the test peptides was necessary, a substantial increase in screening throughput was achieved. Importantly, the peptide conjugates can be used to probe the endogenous receptor in its native environment in vivo.
• Backbone Amide Linker Strategy for the Synthesis of 1,4-Triazole-Containing Cyclic Tetra- and Pentapeptides
  作者：Jasper Springer、Kimberly R. de Cuba、Sandrine Calvet-Vitale、Jan A. J. Geenevasen、Pedro H. H. Hermkens、Henk Hiemstra、Jan H. van Maarseveen

  DOI：10.1002/ejoc.200800143

  日期：2008.5

  A backbone amide linker strategy was chosen for the solid-phase synthesis of triazole-containing Cyclic tetra- and pentapeptides. An alkyne-substituted linker derived from 4-hydroxy-2-methoxybenzaldehyde was elongated by using standard "Fmoc-based" solid phase chemistry and terminated by coupling of an azido acid. In solution, the peptides were cyclized by a Cu-1-catalyzed azide-alkyne cycloaddition

  选择主链酰胺接头策略用于固相合成含三唑的环状四肽和五肽。衍生自 4-羟基-2-甲氧基苯甲醛的炔烃取代的接头通过使用标准的“基于 Fmoc”的固相化学延长并通过偶氮酸的偶联终止。在溶液中，肽通过 Cu-1 催化的叠氮化物-炔环加成反应环化。固体支持的合成线性肽必须在环化之前裂解。作为环状四肽的一个例子，环-[Pro-Val-Pro-Tyr] (2) 的三唑类似物是通过固相/溶液相方法制备的。对于环状五肽，选择 segetalin B (3) 作为模型化合物以显示该方法的适用性。