4-O-β-di-N-acetylchitobiosylmoranoline

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-O-β-di-N-acetylchitobiosylmoranoline
• 英文别名: N-[(2S,3R,4R,5S,6R)-2-[(2R,3S,4R,5R,6R)-5-acetamido-6-[(2R,3R,4R,5S)-4,5-dihydroxy-2-(hydroxymethyl)piperidin-3-yl]oxy-4-hydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide
• 化学式: C₂₂H₃₉N₃O₁₄
• 分子量: 569.563
• InChiKey: ULXPKFHXXUJACF-JZBPHGGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.6
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  269
• 氢给体数：
  11
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  chitotetraose 、 1-脱氧野尻霉素 在 hen egg white lysozyme 作用下， 以 二甲基亚砜 为溶剂， 反应 100.0h， 以36.3%的产率得到4-O-β-N-acetylglucosaminylmoranoline
  参考文献：
  名称：

  A Novel Transition-state Analogue for Lysozyme, 4-O-β-Tri-N-acetylchitotriosyl Moranoline, Provided Evidence Supporting the Covalent Glycosyl-enzyme Intermediate*

  摘要：

  4-O-beta-Di-N-acetylchitobiosyl moranoline (2) and 4-O-beta-tri-N-acetylchitotriosyl moranoline (3) were produced by lysozyme-mediated transglycosylation from the substrates tetra-N-acetylchitotetraose, (GlcNAc)(4), and moranoline, and the binding modes of 2 and 3 to hen egg white lysozyme (HEWL) was examined by inhibition kinetics, isothermal titration calorimetry (ITC), and x-ray crystallography. Compounds 2 and 3 specifically bound to HEWL, acting as competitive inhibitors with K-i values of 2.01 x 10(-5) and 1.84 x 10(-6) M, respectively. From IT Canalysis, the binding of 3 was found to be driven by favorable enthalpy change (Delta H-r degrees), which is similar to those obtained for 2 and (GlcNAc)(4). However, the entropy loss (-T Delta S-r degrees) for the binding of 3 was smaller than those of 2 and (GlcNAc)(4). Thus the binding of 3 was found to be more favorable than those of the others. Judging from the K-d value of 3 (760 nM), the compound appears to have the highest affinity among the lysozyme inhibitors identified to date. X-ray crystal structure of HEWL in a complex with 3 showed that compound 3 binds to subsites -4 to -1 and the moranoline moiety adopts an undistorted C-4(1) chair conformation almost overlapping with the -1 sugar covalently bound to Asp-52 of HEWL (Vocadlo, Davies, G.J., Laine, R., and Withers, S. G. (2001) Nature 412, 835-838). From these results, we concluded that compound 3 serves as a transition-state analogue for lysozyme providing additional evidence supporting the covalent glycosyl-enzyme intermediate in the catalytic reaction.

  DOI：

  10.1074/jbc.m112.439281

文献信息

• A Novel Transition-state Analogue for Lysozyme, 4-O-β-Tri-N-acetylchitotriosyl Moranoline, Provided Evidence Supporting the Covalent Glycosyl-enzyme Intermediate*
  作者：Makoto Ogata、Naoyuki Umemoto、Takayuki Ohnuma、Tomoyuki Numata、Akari Suzuki、Taichi Usui、Tamo Fukamizo

  DOI：10.1074/jbc.m112.439281

  日期：2013.3

  4-O-beta-Di-N-acetylchitobiosyl moranoline (2) and 4-O-beta-tri-N-acetylchitotriosyl moranoline (3) were produced by lysozyme-mediated transglycosylation from the substrates tetra-N-acetylchitotetraose, (GlcNAc)(4), and moranoline, and the binding modes of 2 and 3 to hen egg white lysozyme (HEWL) was examined by inhibition kinetics, isothermal titration calorimetry (ITC), and x-ray crystallography. Compounds 2 and 3 specifically bound to HEWL, acting as competitive inhibitors with K-i values of 2.01 x 10(-5) and 1.84 x 10(-6) M, respectively. From IT Canalysis, the binding of 3 was found to be driven by favorable enthalpy change (Delta H-r degrees), which is similar to those obtained for 2 and (GlcNAc)(4). However, the entropy loss (-T Delta S-r degrees) for the binding of 3 was smaller than those of 2 and (GlcNAc)(4). Thus the binding of 3 was found to be more favorable than those of the others. Judging from the K-d value of 3 (760 nM), the compound appears to have the highest affinity among the lysozyme inhibitors identified to date. X-ray crystal structure of HEWL in a complex with 3 showed that compound 3 binds to subsites -4 to -1 and the moranoline moiety adopts an undistorted C-4(1) chair conformation almost overlapping with the -1 sugar covalently bound to Asp-52 of HEWL (Vocadlo, Davies, G.J., Laine, R., and Withers, S. G. (2001) Nature 412, 835-838). From these results, we concluded that compound 3 serves as a transition-state analogue for lysozyme providing additional evidence supporting the covalent glycosyl-enzyme intermediate in the catalytic reaction.