(sodium 5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosynate)-(2->3)-β-D-galactopyranosyl-(1->3)-1,5-anhydro-6-O-benzyl-2-deoxy-D-lyxo-hexitol | 1123178-44-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (sodium 5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosynate)-(2->3)-β-D-galactopyranosyl-(1->3)-1,5-anhydro-6-O-benzyl-2-deoxy-D-lyxo-hexitol
• 英文别名: sodium;(2S,4S,5R,6R)-5-acetamido-2-[(2R,3S,4S,5R,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-[(2R,3R,4R)-3-hydroxy-2-(phenylmethoxymethyl)oxan-4-yl]oxyoxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylate
• CAS: 1123178-44-8
• 化学式: C₃₀H₄₄NO₁₇*Na
• 分子量: 713.666
• InChiKey: RALLPCORGDJQNX-XLEWEAOUSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -8.62
• 重原子数：
  49
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  286
• 氢给体数：
  9
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  (benzyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosynate)-(2->3)-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1->3)-1,5-anhydro-6-O-benzyl-2-deoxy-D-lyxo-hexitol 在 甲醇 、 sodium methylate 、 水 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以68%的产率得到(sodium 5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosynate)-(2->3)-β-D-galactopyranosyl-(1->3)-1,5-anhydro-6-O-benzyl-2-deoxy-D-lyxo-hexitol
  参考文献：
  名称：

  Examination of the Biological Role of the α(2→6)-Linked Sialic Acid in Gangliosides Binding to the Myelin-Associated Glycoprotein (MAG)

  摘要：

  The tetrasaccharide 1, a substructure of ganglioside GQ1b alpha, shows a remarkable affinity for the myelin-associated glycoprotein (MAG) and was therefore selected as starting point for a lead optimization program. In our search for structurally simplified and pharmacokinetically improved mimics of 1, modifications of the core disaccharide, the alpha(2 -> 3)- and the alpha(2 -> 6)-linked sialic acid were synthesized. Biphenylmethyl and (S)-lactate were identified as suitable replacements for the alpha(2 -> 6)-linked sialic acid. Combined with a core modification and the earlier found aryl amide substituent in the 9-position of the alpha(2 -> 3)-linked sialic acid, high affinity MAG antagonists were identified. All mimics were tested in a competitive target-based binding assay, providing relative inhibitory potencies (rlP). Compared to the reference tetrasaccharide 1, the rIPs of the most potent antagonists 59 and 60 are enhanced nearly 400-fold. Their K(D)s determined in surface plasmon resonance experiments are in the low micromolar range. These results are in semiquantitative agreement with molecular modeling studies. This new class of glycomimetics will allow to validate the role of MAG in the axon regeneration process.

  DOI：

  10.1021/jm801058n

文献信息

• Examination of the Biological Role of the α(2→6)-Linked Sialic Acid in Gangliosides Binding to the Myelin-Associated Glycoprotein (MAG)
  作者：Oliver Schwardt、Heiko Gäthje、Angelo Vedani、Stefanie Mesch、Gan-Pan Gao、Morena Spreafico、Johannes von Orelli、Sørge Kelm、Beat Ernst

  DOI：10.1021/jm801058n

  日期：2009.2.26

  The tetrasaccharide 1, a substructure of ganglioside GQ1b alpha, shows a remarkable affinity for the myelin-associated glycoprotein (MAG) and was therefore selected as starting point for a lead optimization program. In our search for structurally simplified and pharmacokinetically improved mimics of 1, modifications of the core disaccharide, the alpha(2 -> 3)- and the alpha(2 -> 6)-linked sialic acid were synthesized. Biphenylmethyl and (S)-lactate were identified as suitable replacements for the alpha(2 -> 6)-linked sialic acid. Combined with a core modification and the earlier found aryl amide substituent in the 9-position of the alpha(2 -> 3)-linked sialic acid, high affinity MAG antagonists were identified. All mimics were tested in a competitive target-based binding assay, providing relative inhibitory potencies (rlP). Compared to the reference tetrasaccharide 1, the rIPs of the most potent antagonists 59 and 60 are enhanced nearly 400-fold. Their K(D)s determined in surface plasmon resonance experiments are in the low micromolar range. These results are in semiquantitative agreement with molecular modeling studies. This new class of glycomimetics will allow to validate the role of MAG in the axon regeneration process.