Methyl 6-oxo-6-[(4-sulfamoylphenyl)methylamino]hexanoate | 928211-28-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Methyl 6-oxo-6-[(4-sulfamoylphenyl)methylamino]hexanoate
• CAS: 928211-28-3
• 化学式: C₁₄H₂₀N₂O₅S
• 分子量: 328.389
• InChiKey: HLPABDMNZAWAIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Methyl 6-oxo-6-[(4-sulfamoylphenyl)methylamino]hexanoate 在 lithium hydroxide 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.17h， 生成 {2-[5-(4-sulfamoyl-benzylcarbamoyl)-pentanoylamino]-ethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Dependence of Effective Molarity on Linker Length for an Intramolecular Protein−Ligand System

  摘要：

  This paper reports dissociation constants and "effective molarities" (M-eff) for the intramolecular binding of a ligand covalently attached to the surface of a protein by oligo(ethylene glycol) (EG(n)) linkers of different lengths (n = 0, 2, 5, 10, and 20) and compares these experimental values with theoretical estimates from polymer theory. As expected, the value of M-eff is lowest when the linker is too short (n = 0) to allow the ligand to bind noncovalently at the active site of the protein without strain, is highest when the linker is the optimal length (n = 2) to allow such binding to occur, and decreases monotonically as the length increases past this optimal value (but only by a factor of similar to 8 from n = 2 to n = 20). These experimental results are not compatible with a model in which the single bonds of the linker are completely restricted when the ligand has bound noncovalently to the active site of the protein, but they are quantitatively compatible with a model that treats the linker as a random-coil polymer. Calorimetry revealed that enthalpic interactions between the linker and the protein are not important in determining the thermodynamics of the system. Taken together, these results suggest that the manifestation of the linker in the thermodynamics of binding is exclusively entropic. The values of M-eff are, theoretically, intrinsic properties of the EG(n) linkers and can be used to predict the avidities of multivalent ligands with these linkers for multivalent proteins. The weak dependence of M-eff on linker length suggests that multivalent ligands containing flexible linkers that are longer than the spacing between the binding sites of a multivalent protein will be effective in binding, and that the use of flexible linkers with lengths somewhat greater than the optimal distance between binding sites is a justifiable strategy for the design of multivalent ligands.

  DOI：

  10.1021/ja066780e
• 作为产物：
  描述：

  甲基脂肪酰氯 、 mafenide hydrochloride 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以95%的产率得到Methyl 6-oxo-6-[(4-sulfamoylphenyl)methylamino]hexanoate
  参考文献：
  名称：

  使用亲和毛细管电泳确定芳基磺酰胺与牛碳酸酐酶结合的动力学和平衡常数。

  摘要：

  亲和毛细管电泳（ACE）提供了一种研究蛋白质-配体相互作用的新方法。ACE的基础是蛋白质与其配体形成复合物时其电泳迁移率的变化。可以直接对带电荷的配体定量该结合相互作用，或与先前表征的带电荷的配体竞争间接对中性配体进行定量。使用ACE确定动力学常数和平衡常数仅取决于蛋白质的迁移时间和峰形（而不是峰面积）的变化。在ACE条件下对蛋白质迁移率的模拟表明，实验获得的电泳图可以用以下几个变量来解释：打开和关闭的速率（因此，结合常数），配体的浓度，

  DOI：

  10.1021/jm00053a016

文献信息

• Use of affinity capillary electrophoresis to determine kinetic and equilibrium constants for binding of arylsulfonamides to bovine carbonic anhydrase
  作者：Luis Z. Avila、Yen Ho Chu、Erich C. Blossey、George M. Whitesides

  DOI：10.1021/jm00053a016

  日期：1993.1

  Determination of kinetic and equilibrium constants using ACE relies only on the changes in the migration time and shape (but not the area) of the peak due to protein. Simulation of the protein mobility under conditions of ACE suggests that the experimentally obtained electropherograms can be explained in terms of few variables: on and off rates (and thus, binding constant), concentration of the ligand(s)

  亲和毛细管电泳（ACE）提供了一种研究蛋白质-配体相互作用的新方法。ACE的基础是蛋白质与其配体形成复合物时其电泳迁移率的变化。可以直接对带电荷的配体定量该结合相互作用，或与先前表征的带电荷的配体竞争间接对中性配体进行定量。使用ACE确定动力学常数和平衡常数仅取决于蛋白质的迁移时间和峰形（而不是峰面积）的变化。在ACE条件下对蛋白质迁移率的模拟表明，实验获得的电泳图可以用以下几个变量来解释：打开和关闭的速率（因此，结合常数），配体的浓度，
• Dependence of Effective Molarity on Linker Length for an Intramolecular Protein−Ligand System
  作者：Vijay M. Krishnamurthy、Vincent Semetey、Paul J. Bracher、Nan Shen、George M. Whitesides

  DOI：10.1021/ja066780e

  日期：2007.2.1

  This paper reports dissociation constants and "effective molarities" (M-eff) for the intramolecular binding of a ligand covalently attached to the surface of a protein by oligo(ethylene glycol) (EG(n)) linkers of different lengths (n = 0, 2, 5, 10, and 20) and compares these experimental values with theoretical estimates from polymer theory. As expected, the value of M-eff is lowest when the linker is too short (n = 0) to allow the ligand to bind noncovalently at the active site of the protein without strain, is highest when the linker is the optimal length (n = 2) to allow such binding to occur, and decreases monotonically as the length increases past this optimal value (but only by a factor of similar to 8 from n = 2 to n = 20). These experimental results are not compatible with a model in which the single bonds of the linker are completely restricted when the ligand has bound noncovalently to the active site of the protein, but they are quantitatively compatible with a model that treats the linker as a random-coil polymer. Calorimetry revealed that enthalpic interactions between the linker and the protein are not important in determining the thermodynamics of the system. Taken together, these results suggest that the manifestation of the linker in the thermodynamics of binding is exclusively entropic. The values of M-eff are, theoretically, intrinsic properties of the EG(n) linkers and can be used to predict the avidities of multivalent ligands with these linkers for multivalent proteins. The weak dependence of M-eff on linker length suggests that multivalent ligands containing flexible linkers that are longer than the spacing between the binding sites of a multivalent protein will be effective in binding, and that the use of flexible linkers with lengths somewhat greater than the optimal distance between binding sites is a justifiable strategy for the design of multivalent ligands.