phenyl 2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-benzyl-α-D-glucopyranosyl-(1->3)-2,4,6-tri-O-benzyl-1-thio-α-D-mannopyranoside | 1332524-22-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: phenyl 2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-benzyl-α-D-glucopyranosyl-(1->3)-2,4,6-tri-O-benzyl-1-thio-α-D-mannopyranoside
• CAS: 1332524-22-7
• 化学式: C₉₄H₉₆O₁₅S
• 分子量: 1497.85
• InChiKey: WIWQFLGXRKJRPQ-VTCGWUCRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  17.47
• 重原子数：
  110.0
• 可旋转键数：
  39.0
• 环数：
  14.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  138.45
• 氢给体数：
  0.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  phenyl 2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-benzyl-α-D-glucopyranosyl-(1->3)-2,4,6-tri-O-benzyl-1-thio-α-D-mannopyranoside 在 N-溴代丁二酰亚胺(NBS) 、 水 作用下， 以 丙酮 为溶剂， 反应 2.0h， 以100%的产率得到
  参考文献：
  名称：

  Convergent Synthesis of Homogeneous Glc₁Man₉GlcNAc₂-Protein and Derivatives as Ligands of Molecular Chaperones in Protein Quality Control

  摘要：

  A detailed understanding of the molecular mechanism of chaperone-assisted protein quality control is often hampered by the lack of well-defined homogeneous glycoprotein probes. We describe here a highly convergent chemoenzymatic synthesis of the monoglucosylated glycoforms of bovine ribonuclease (RNase) as specific ligands of lectin-like chaperones calnexin (CNX) and calreticulin (CRT) that are known to recognize the monoglucosylated high-mannose oligosaccharide component of glycoproteins in protein folding. The synthesis of a selectively modified glycoform Gal(1)Glc(1)Man(9)GlcNAc(2)-RNase was accomplished by chemical synthesis of a large N-glycan oxazoline and its subsequent enzymatic ligation to GlcNAc-RNase under the catalysis of a glycosynthase. Selective removal of the terminal galactose by a beta-galactosidase gave the Glc(1)Man(9)GlcNAc(2)-RNase glycoform in excellent yield. CD spectroscopic analysis and RNA-hydrolyzing assay indicated that the synthetic RNase glycoforms maintained essentially the same global conformations and were fully active as the natural bovine ribonudease B. SPR binding studies revealed that the Glc(1)Man(9)GlcNAc(2)-RNase had high affinity to lectin CRT, while the synthetic Man(9)GlcNAc(2)-RNase glycoform and natural RNase B did not show CRT-binding activity. These results confirmed the essential role of the glucose moiety in the chaperone molecular recognition. Interestingly, the galactose-masked glycoform Gal(1)Glc(1)Man(9)GlcNAc(2)-RNase also showed significant affinity to lectin CRT, suggesting that a galactose beta-1,4-linked to the key glucose moiety does not significantly block the lectin binding. These synthetic homogeneous glycoprotein probes should be valuable for a detailed mechanistic study on how molecular chaperones work in concert to distinguish between misfolded and folded glycoproteins in the protein quality control cycle.

  DOI：

  10.1021/ja204831z
• 作为产物：
  描述：

  2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-benzyl-β-D-glucopyranosyl fluoride 、 phenyl 2,4,6-tri-O-benzyl-1-thio-α-D-mannopyranoside 在 2,6-二叔丁基-4-甲基吡啶 、 Cp2Zr(OTf)2 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 5.5h， 以68%的产率得到phenyl 2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl-(1->4)-2,3,6-tri-O-benzyl-α-D-glucopyranosyl-(1->3)-2,4,6-tri-O-benzyl-1-thio-α-D-mannopyranoside
  参考文献：
  名称：

  Convergent Synthesis of Homogeneous Glc₁Man₉GlcNAc₂-Protein and Derivatives as Ligands of Molecular Chaperones in Protein Quality Control

  摘要：

  A detailed understanding of the molecular mechanism of chaperone-assisted protein quality control is often hampered by the lack of well-defined homogeneous glycoprotein probes. We describe here a highly convergent chemoenzymatic synthesis of the monoglucosylated glycoforms of bovine ribonuclease (RNase) as specific ligands of lectin-like chaperones calnexin (CNX) and calreticulin (CRT) that are known to recognize the monoglucosylated high-mannose oligosaccharide component of glycoproteins in protein folding. The synthesis of a selectively modified glycoform Gal(1)Glc(1)Man(9)GlcNAc(2)-RNase was accomplished by chemical synthesis of a large N-glycan oxazoline and its subsequent enzymatic ligation to GlcNAc-RNase under the catalysis of a glycosynthase. Selective removal of the terminal galactose by a beta-galactosidase gave the Glc(1)Man(9)GlcNAc(2)-RNase glycoform in excellent yield. CD spectroscopic analysis and RNA-hydrolyzing assay indicated that the synthetic RNase glycoforms maintained essentially the same global conformations and were fully active as the natural bovine ribonudease B. SPR binding studies revealed that the Glc(1)Man(9)GlcNAc(2)-RNase had high affinity to lectin CRT, while the synthetic Man(9)GlcNAc(2)-RNase glycoform and natural RNase B did not show CRT-binding activity. These results confirmed the essential role of the glucose moiety in the chaperone molecular recognition. Interestingly, the galactose-masked glycoform Gal(1)Glc(1)Man(9)GlcNAc(2)-RNase also showed significant affinity to lectin CRT, suggesting that a galactose beta-1,4-linked to the key glucose moiety does not significantly block the lectin binding. These synthetic homogeneous glycoprotein probes should be valuable for a detailed mechanistic study on how molecular chaperones work in concert to distinguish between misfolded and folded glycoproteins in the protein quality control cycle.

  DOI：

  10.1021/ja204831z