6-(4-butyl-1H-1,2,3-triazol-1-yl)hexanoic acid | 1242657-87-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 6-(4-butyl-1H-1,2,3-triazol-1-yl)hexanoic acid
• 英文别名: 6-(4-Butyltriazol-1-yl)hexanoic acid
• CAS: 1242657-87-9
• 化学式: C₁₂H₂₁N₃O₂
• 分子量: 239.318
• InChiKey: FZAKSRAJTAZIMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  68
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4-butyl-1H-1,2,3-triazol-1-yl)hexanoic acid 、 Fmoc-L-苯丙氨酸 、 Fmoc-L-天冬氨酸 beta-叔丁酯 、 Fmoc-L-蛋氨酸 、 Fmoc-L-色氨酸(Boc)-OH 在 6-氯-1-羟基苯并三氮唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.03h， 生成 (3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-[6-(4-butyltriazol-1-yl)hexanoylamino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-oxobutanoic acid
  参考文献：
  名称：

  A sucrose-derived scaffold for multimerization of bioactive peptides

  摘要：

  A spherical molecular scaffold bearing eight terminal alkyne groups was synthesized in one step from sucrose. One or more copies of a tetrapeptide azide, either N-3(CH2)(5)(C=O)-His-DPhe-Arg-Trp-NH2 (MSH4) or N-3(CH2)(5)(C=O)-Trp-Met-Asp-Phe-NH2 (CCK4), were attached to the scaffold via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Competitive binding assays using Eu-labeled probes based on the superpotent ligands Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 (NDP-alpha-MSH) and Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2 (CCK8) were used to study the interactions of monovalent and multivalent MSH4 and CCK4 constructs with Hek293 cells engineered to overexpress MC4R and CCK2R. All of the monovalent and multivalent MSH4 constructs exhibited binding comparable to that of the parental ligand, suggesting that either the ligand spacing was inappropriate for multivalent binding, or MSH4 is too weak a binder for a second 'anchoring' binding event to occur before the monovalently-bound construct is released from the cell surface. In contrast with this behavior, monovalent CCK4 constructs were significantly less potent than the parental ligand, while multivalent CCK4 constructs were as or more potent than the parental ligand. These results are suggestive of multivalent binding, which may be due to increased residence times for monovalently bound CCK4 constructs on the cell surface relative to MSH4 constructs, the greater residence time being necessary for the establishment of multivalent binding. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.053
• 作为产物：
  描述：

  6-叠氮基己酸 、 1-己炔 在 sodium ascorbate 、 copper(II) sulfate 作用下， 以 水 、 叔丁醇 为溶剂， 以60%的产率得到6-(4-butyl-1H-1,2,3-triazol-1-yl)hexanoic acid
  参考文献：
  名称：

  用于生物活性肽多聚化的茄尼醇衍生支架

  摘要：

  从茄尼醇中分五步合成了带有不同数量末端炔基的柔性分子支架。R(CO)-MSH(4)-NH 2配体与人类黑皮质素 4 受体 (hMC4R) 的结合亲和力相对较低，通过固相合成制备，并用 6-叠氮己酸进行 N-末端酰化。多个拷贝的叠氮化物 N 3 (CH 2 ) 5 (CO)-MSH(4)-NH 2通过铜 (I) 催化的叠氮化物-炔烃环加成反应 (CuAAC ） 反应。对照研究表明，含三唑的配体 CH 3 (CH 2 ) 3 (C2 N 3 )(CH 2 ) 5 (CO)-MSH(4)-NH 2相对于相应的母体配体CH 3 (CO)-MSH(4)-NH 2没有显着减少。在使用基于超强配体 NDP-α-MSH 的 Eu 标记探针进行的竞争性结合测定中，单价和多价构建体似乎以单价形式与 hMC4R 结合。在使用基于 MSH(4) 的 Eu 标记探针进行的类似测定中，观察到每个支架的 MSH(4) 含量增加时结合效力适度增加。

  DOI：

  10.1021/jo101043m

文献信息

• A sucrose-derived scaffold for multimerization of bioactive peptides
  作者：Venkataramanarao Rao、Ramesh Alleti、Liping Xu、Narges K. Tafreshi、David L. Morse、Robert J. Gillies、Eugene A. Mash

  DOI：10.1016/j.bmc.2011.08.053

  日期：2011.11

  A spherical molecular scaffold bearing eight terminal alkyne groups was synthesized in one step from sucrose. One or more copies of a tetrapeptide azide, either N-3(CH2)(5)(C=O)-His-DPhe-Arg-Trp-NH2 (MSH4) or N-3(CH2)(5)(C=O)-Trp-Met-Asp-Phe-NH2 (CCK4), were attached to the scaffold via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Competitive binding assays using Eu-labeled probes based on the superpotent ligands Ser-Tyr-Ser-Nle-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2 (NDP-alpha-MSH) and Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2 (CCK8) were used to study the interactions of monovalent and multivalent MSH4 and CCK4 constructs with Hek293 cells engineered to overexpress MC4R and CCK2R. All of the monovalent and multivalent MSH4 constructs exhibited binding comparable to that of the parental ligand, suggesting that either the ligand spacing was inappropriate for multivalent binding, or MSH4 is too weak a binder for a second 'anchoring' binding event to occur before the monovalently-bound construct is released from the cell surface. In contrast with this behavior, monovalent CCK4 constructs were significantly less potent than the parental ligand, while multivalent CCK4 constructs were as or more potent than the parental ligand. These results are suggestive of multivalent binding, which may be due to increased residence times for monovalently bound CCK4 constructs on the cell surface relative to MSH4 constructs, the greater residence time being necessary for the establishment of multivalent binding. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and Characterization of Time-resolved Fluorescence Probes for Evaluation of Competitive Binding to Melanocortin Receptors
  作者：Ramesh Alleti、Josef Vagner、Dilani Chathurika Dehigaspitiya、Valerie E. Moberg、N.G.R.D. Elshan、Narges K. Tafreshi、Nabila Brabez、Craig S. Weber、Ronald M. Lynch、Victor J. Hruby、Robert J. Gillies、David L. Morse、Eugene A. Mash

  DOI：10.1016/j.bmc.2013.06.052

  日期：2013.9

  Probes for use in time-resolved fluorescence competitive binding assays at melanocortin receptors based on the parental ligands MSH(4), MSH(7), and NDP-alpha-MSH were prepared by solid phase synthesis methods, purified, and characterized. The saturation binding of these probes was studied using HEK-293 cells engineered to overexpress the human melanocortin 4 receptor (hMC4R) as well as the human cholecystokinin 2 receptor (hCCK2R). The ratios of non-specific binding to total binding approached unity at high concentrations for each probe. At low probe concentrations, receptor-mediated binding and uptake was discernable, and so probe concentrations were kept as low as possible in determining K-d values. The Eu-DTPA-PEGO-MSH(4) probe exhibited low specific binding relative to non-specific binding, even at low nanomolar concentrations, and was deemed unsuitable for use in competition binding assays. The Eu-DTPA-PEGO probes based on MSH(7) and NDP-alpha-MSH exhibited K-d values of 27 +/- 3.9 nM and 4.2 +/- 0.48 nM, respectively, for binding with hMC4R. These probes were employed in competitive binding assays to characterize the interactions of hMC4R with monovalent and divalent MSH(4), MSH(7), and NDP-alpha-MSH constructs derived from squalene. Results from assays with both probes reflected only statistical enhancements, suggesting improper ligand spacing on the squalene scaffold for the divalent constructs. The K-i values from competitive binding assays that employed the MSH(7)-based probe were generally lower than the K-i values obtained when the probe based on NDP-alpha-MSH was employed, which is consistent with the greater potency of the latter probe. The probe based on MSH(7) was also competed with monovalent, divalent, and trivalent MSH(4) constructs that previously demonstrated multivalent binding in competitive binding assays against a variant of the probe based on NDP-alpha-MSH. Results from these assays confirm multivalent binding, but suggest a more modest increase in avidity for these MSH(4) constructs than was previously reported. (C) 2013 Elsevier Ltd. All rights reserved.
• A Solanesol-Derived Scaffold for Multimerization of Bioactive Peptides
  作者：Ramesh Alleti、Venkataramanarao Rao、Liping Xu、Robert J. Gillies、Eugene A. Mash

  DOI：10.1021/jo101043m

  日期：2010.9.3

  from solanesol. R(CO)-MSH(4)-NH2 ligands, which have a relatively low affinity for binding at the human melanocortin 4 receptor (hMC4R), were prepared by solid phase synthesis and were N-terminally acylated with 6-azidohexanoic acid. Multiple copies of the azide N3(CH2)5(CO)-MSH(4)-NH2 were attached to the alkyne-bearing, solanesol-derived molecular scaffold via the copper(I)-catalyzed azide−alkyne cycloaddition

  从茄尼醇中分五步合成了带有不同数量末端炔基的柔性分子支架。R(CO)-MSH(4)-NH 2配体与人类黑皮质素 4 受体 (hMC4R) 的结合亲和力相对较低，通过固相合成制备，并用 6-叠氮己酸进行 N-末端酰化。多个拷贝的叠氮化物 N 3 (CH 2 ) 5 (CO)-MSH(4)-NH 2通过铜 (I) 催化的叠氮化物-炔烃环加成反应 (CuAAC ） 反应。对照研究表明，含三唑的配体 CH 3 (CH 2 ) 3 (C2 N 3 )(CH 2 ) 5 (CO)-MSH(4)-NH 2相对于相应的母体配体CH 3 (CO)-MSH(4)-NH 2没有显着减少。在使用基于超强配体 NDP-α-MSH 的 Eu 标记探针进行的竞争性结合测定中，单价和多价构建体似乎以单价形式与 hMC4R 结合。在使用基于 MSH(4) 的 Eu 标记探针进行的类似测定中，观察到每个支架的 MSH(4) 含量增加时结合效力适度增加。