3,4-di-{[methyl 4-O-(α-D-galactopyranosyl)-β-D-galactopyranoside-2-yloxy]ethylamino}-3-cyclobutene-1,2-dione

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,4-di-{[methyl 4-O-(α-D-galactopyranosyl)-β-D-galactopyranoside-2-yloxy]ethylamino}-3-cyclobutene-1,2-dione
• 英文别名: 3,4-bis[2-[(2R,3R,4S,5R,6R)-4-hydroxy-6-(hydroxymethyl)-2-methoxy-5-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-3-yl]oxyethylamino]cyclobut-3-ene-1,2-dione
• 化学式: C₃₄H₅₆N₂O₂₄
• 分子量: 876.818
• InChiKey: GAADBEDAXOZVKJ-IOIHLGAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.8
• 重原子数：
  60
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  393
• 氢给体数：
  14
• 氢受体数：
  26

反应信息

• 作为产物：
  描述：

  Methyl 3,6-di-O-benzyl-2-O-[2-(methylsulfonyloxy)ethyl]-4-O-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-β-D-galactopyranoside 在 palladium dihydroxide sodium azide 、 氢气 、 四丁基碘化铵 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 3,4-di-{[methyl 4-O-(α-D-galactopyranosyl)-β-D-galactopyranoside-2-yloxy]ethylamino}-3-cyclobutene-1,2-dione
  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

• Optimization of Tether Length in Nonglycosidically Linked Bivalent Ligands That Target Sites 2 and 1 of a <i>Shiga</i>-like Toxin
  作者：Pavel I. Kitov、Hiroki Shimizu、Steven W. Homans、David R. Bundle

  DOI：10.1021/ja0258529

  日期：2003.3.1

  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.