methyl 4-O-[3,6-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-2-O-[2-(4-nitrophenyloxycarbonylethyl)ethyl]-β-D-galactopyranosyl]-2,3,6-tri-O-benzyl-β-D-glucopyranoside | 244077-02-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 4-O-[3,6-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-2-O-[2-(4-nitrophenyloxycarbonylethyl)ethyl]-β-D-galactopyranosyl]-2,3,6-tri-O-benzyl-β-D-glucopyranoside
• 英文别名: 2-[(2S,3R,4S,5S,6R)-2-[(2R,3R,4S,5R,6R)-6-methoxy-4,5-bis(phenylmethoxy)-2-(phenylmethoxymethyl)oxan-3-yl]oxy-4-phenylmethoxy-6-(phenylmethoxymethyl)-5-[(2R,3R,4S,5S,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]oxyoxan-3-yl]oxyethyl (4-nitrophenyl) carbonate
• CAS: 244077-02-9
• 化学式: C₉₁H₉₅NO₂₁
• 分子量: 1538.75
• InChiKey: KRZUSFGDRQILHK-QSVDRDRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.6
• 重原子数：
  113
• 可旋转键数：
  42
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  229
• 氢给体数：
  0
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  1,3-丙二胺 、 methyl 4-O-[3,6-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-2-O-[2-(4-nitrophenyloxycarbonylethyl)ethyl]-β-D-galactopyranosyl]-2,3,6-tri-O-benzyl-β-D-glucopyranoside 以 四氢呋喃 为溶剂， 反应 3.0h， 以92.5%的产率得到N,N'-bis{{methyl 4-O-[3,6-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-β-D-galactopyranosyl]-2,3,6-tri-O-benzyl-β-D-glucopyranoside}-2'-yloxyethyl}oxycarbonylpropylenediamine
  参考文献：
  名称：

  Optimization of Tether Length in Nonglycosidically Linked Bivalent Ligands That Target Sites 2 and 1 of a Shiga-like Toxin

  摘要：

  A series of bivalent ligands for a Shiga-like toxin have been synthesized, their experimentally determined inhibitory activities were compared with a simplified thermodynamic model, and computer simulations were used to predict the optimal tether length in bivalent ligands. The design of the inhibitors exploits the proximity of the C-2' hydroxyl groups of two P-k-trisaccharides when bound to two different, neighboring carbohydrate recognizing binding sites located on the surface of Shiga-like toxin. NMR studies of the complex between the toxin and bivalent ligands show that site 2 and site 1 of a single B subunit are simultaneously occupied by a tethered P-k-trisaccharide dimer. A simplified thermodynamic treatment provides the intrinsic affinities and binding energies for the intermolecular and intramolecular association events and permits the deconvolution of the contributions to the relative binding energies for the set of bivalent ligands. Conformational analysis based on MD simulations for bivalent galabioside dimers containing different tethers demonstrated that the calculated local concentrations of the pendant ligand at the second binding site correlate with the experimentally determined relative affinity values of the respective bivalent ligands, thereby providing a predictive method to optimize tether length.

  DOI：

  10.1021/ja0258529
• 作为产物：
  描述：

  对硝基苯基氯甲酸酯 、 methyl 4-O-[3,6-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-2-O-(2-hydroxyethyl)-β-D-galactopyranosyl]-2,3,6-tri-O-benzyl-β-D-glucopyranoside 在 吡啶 作用下， 反应 4.0h， 以85%的产率得到methyl 4-O-[3,6-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-2-O-[2-(4-nitrophenyloxycarbonylethyl)ethyl]-β-D-galactopyranosyl]-2,3,6-tri-O-benzyl-β-D-glucopyranoside
  参考文献：
  名称：

  Optimization of Tether Length in Nonglycosidically Linked Bivalent Ligands That Target Sites 2 and 1 of a Shiga-like Toxin

  摘要：

  A series of bivalent ligands for a Shiga-like toxin have been synthesized, their experimentally determined inhibitory activities were compared with a simplified thermodynamic model, and computer simulations were used to predict the optimal tether length in bivalent ligands. The design of the inhibitors exploits the proximity of the C-2' hydroxyl groups of two P-k-trisaccharides when bound to two different, neighboring carbohydrate recognizing binding sites located on the surface of Shiga-like toxin. NMR studies of the complex between the toxin and bivalent ligands show that site 2 and site 1 of a single B subunit are simultaneously occupied by a tethered P-k-trisaccharide dimer. A simplified thermodynamic treatment provides the intrinsic affinities and binding energies for the intermolecular and intramolecular association events and permits the deconvolution of the contributions to the relative binding energies for the set of bivalent ligands. Conformational analysis based on MD simulations for bivalent galabioside dimers containing different tethers demonstrated that the calculated local concentrations of the pendant ligand at the second binding site correlate with the experimentally determined relative affinity values of the respective bivalent ligands, thereby providing a predictive method to optimize tether length.

  DOI：

  10.1021/ja0258529

文献信息

• On the Nature of the Multivalency Effect:  A Thermodynamic Model
  作者：Pavel I. Kitov、David R. Bundle

  DOI：10.1021/ja038223n

  日期：2003.12.1

  A quantitative model is proposed for the analysis of the thermodynamic parameters of multivalent interactions in dilute solutions or with immobilized multimeric receptor. The model takes into account all bound species and describes multivalent binding via two microscopic binding energies corresponding to inter- and intramolecular interactions (DeltaGdegrees(inter) and DeltaGdegrees(intra)), the relative contributions of which depend on the distribution of complexes with different numbers of occupied binding sites. The third component of the overall free energy, which we call the "avidity entropy" term, is a function of the degeneracy of bound states, Omega(i), which is calculated on the basis of the topology of interaction and the distribution of all bound species. This term grows rapidly with the number of receptor sites and ligand multivalency, it always favors binding, and explains why multivalency can overcome the loss of conformational entropy when ligands displayed at the ends of long tethers are bound. The microscopic parameters DeltaGdegrees(inter) and DeltadegreesG(intra) may be determined from the observed binding energies for a set of oligovalent ligands by nonlinear fitting with the theoretical model. Here binding data obtained from two series of oligovalent carbohydrate inhibitors for Shiga-like toxins were used to verify the theory. The decavalent and octavalent inhibitors exhibit subnanomolar activity and are the most active soluble inhibitors yet seen that block Shiga-like toxin binding to its native receptor. The theory developed here in conjunction with our protocol for the optimization of tether length provides a predictive approach to design and maximize the avidity of multivalent ligands.