methyl 2-acetylamino-2-deoxy-3-Omethyl-α-D-mannopyranoside | 42756-64-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2-acetylamino-2-deoxy-3-Omethyl-α-D-mannopyranoside
• 英文别名: Methyl 2-acetamido-2-deoxy-4-O-methyl-α-D-mannopyranosid；N-[(2S,3S,4R,5S,6R)-5-hydroxy-6-(hydroxymethyl)-2,4-dimethoxyoxan-3-yl]acetamide
• CAS: 42756-64-9
• 化学式: C₁₀H₁₉NO₆
• 分子量: 249.264
• InChiKey: NQZUQHYRSVKBRT-ZOZBQHSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  97.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-acetylamino-2-deoxy-3-Omethyl-α-D-mannopyranoside 、 乙酸酐 以 吡啶 为溶剂， 以91%的产率得到
  参考文献：
  名称：

  A Novel Approach to Decrease Sialic Acid Expression in Cells by a C-3-modified N-Acetylmannosamine

  摘要：

  Background: Inhibitors of cellular sialic acid expression offer substantial therapeutic promise for diseases associated with oversialylation. Results: 2-Acetylamino-2-deoxy-3-O-methyl-d-mannose reduces the sialic acid concentration in cells and inhibits the UDP-GlcNAc-2-epimerase/ManNAc kinase. Conclusion: Inhibition of the key enzyme of sialic acid biosynthesis by a ManNAc analog decreases cellular sialic acid expression. Significance: ManNAc analogs represent a new class of sialic acid inhibitors.Due to its position at the outermost of glycans, sialic acid is involved in a myriad of physiological and pathophysiological cell functions such as host-pathogen interactions, immune regulation, and tumor evasion. Inhibitors of cell surface sialylation could be a useful tool in cancer, immune, antibiotic, or antiviral therapy. In this work, four different C-3 modified N-acetylmannosamine analogs were tested as potential inhibitors of cell surface sialylation. Peracetylated 2-acetylamino-2-deoxy-3-O-methyl-d-mannose decreases cell surface sialylation in Jurkat cells in a dose-dependent manner up to 80%, quantified by flow cytometry and enzyme-linked lectin assays. High-performance liquid chromatography experiments revealed that not only the concentration of membrane bound but also of cytosolic sialic acid is reduced in treated cells. We have strong evidence that the observed reduction of sialic acid expression in cells is caused by the inhibition of the bifunctional enzyme UDP-GlcNAc-2-epimerase/ManNAc kinase. 2-Acetylamino-2-deoxy-3-O-methyl-d-mannose inhibits the human ManNAc kinase domain of the UDP-GlcNAc-2-epimerase/ManNAc kinase. Binding kinetics of the inhibitor and human N-acetylmannosamine kinase were evaluated using surface plasmon resonance. Specificity studies with human N-acetylglucosamine kinase and hexokinase IV indicated a high specificity of 2-acetylamino-2-deoxy-3-O-methyl-d-mannose for MNK. This substance represents a novel class of inhibitors of sialic acid expression in cells, targeting the key enzyme of sialic acid de novo biosynthesis.

  DOI：

  10.1074/jbc.m114.608398
• 作为产物：
  描述：

  Methyl 2-azido-2-deoxy-4,6-O-(phenylmethylene)-α-D-mannopyranoside 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 2-acetylamino-2-deoxy-3-Omethyl-α-D-mannopyranoside
  参考文献：
  名称：

  A Novel Approach to Decrease Sialic Acid Expression in Cells by a C-3-modified N-Acetylmannosamine

  摘要：

  Background: Inhibitors of cellular sialic acid expression offer substantial therapeutic promise for diseases associated with oversialylation. Results: 2-Acetylamino-2-deoxy-3-O-methyl-d-mannose reduces the sialic acid concentration in cells and inhibits the UDP-GlcNAc-2-epimerase/ManNAc kinase. Conclusion: Inhibition of the key enzyme of sialic acid biosynthesis by a ManNAc analog decreases cellular sialic acid expression. Significance: ManNAc analogs represent a new class of sialic acid inhibitors.Due to its position at the outermost of glycans, sialic acid is involved in a myriad of physiological and pathophysiological cell functions such as host-pathogen interactions, immune regulation, and tumor evasion. Inhibitors of cell surface sialylation could be a useful tool in cancer, immune, antibiotic, or antiviral therapy. In this work, four different C-3 modified N-acetylmannosamine analogs were tested as potential inhibitors of cell surface sialylation. Peracetylated 2-acetylamino-2-deoxy-3-O-methyl-d-mannose decreases cell surface sialylation in Jurkat cells in a dose-dependent manner up to 80%, quantified by flow cytometry and enzyme-linked lectin assays. High-performance liquid chromatography experiments revealed that not only the concentration of membrane bound but also of cytosolic sialic acid is reduced in treated cells. We have strong evidence that the observed reduction of sialic acid expression in cells is caused by the inhibition of the bifunctional enzyme UDP-GlcNAc-2-epimerase/ManNAc kinase. 2-Acetylamino-2-deoxy-3-O-methyl-d-mannose inhibits the human ManNAc kinase domain of the UDP-GlcNAc-2-epimerase/ManNAc kinase. Binding kinetics of the inhibitor and human N-acetylmannosamine kinase were evaluated using surface plasmon resonance. Specificity studies with human N-acetylglucosamine kinase and hexokinase IV indicated a high specificity of 2-acetylamino-2-deoxy-3-O-methyl-d-mannose for MNK. This substance represents a novel class of inhibitors of sialic acid expression in cells, targeting the key enzyme of sialic acid de novo biosynthesis.

  DOI：

  10.1074/jbc.m114.608398

文献信息

• A Novel Approach to Decrease Sialic Acid Expression in Cells by a C-3-modified N-Acetylmannosamine
  作者：Paul R. Wratil、Stephan Rigol、Barbara Solecka、Guido Kohla、Christoph Kannicht、Werner Reutter、Athanassios Giannis、Long D. Nguyen

  DOI：10.1074/jbc.m114.608398

  日期：2014.11

  Background: Inhibitors of cellular sialic acid expression offer substantial therapeutic promise for diseases associated with oversialylation. Results: 2-Acetylamino-2-deoxy-3-O-methyl-d-mannose reduces the sialic acid concentration in cells and inhibits the UDP-GlcNAc-2-epimerase/ManNAc kinase. Conclusion: Inhibition of the key enzyme of sialic acid biosynthesis by a ManNAc analog decreases cellular sialic acid expression. Significance: ManNAc analogs represent a new class of sialic acid inhibitors.Due to its position at the outermost of glycans, sialic acid is involved in a myriad of physiological and pathophysiological cell functions such as host-pathogen interactions, immune regulation, and tumor evasion. Inhibitors of cell surface sialylation could be a useful tool in cancer, immune, antibiotic, or antiviral therapy. In this work, four different C-3 modified N-acetylmannosamine analogs were tested as potential inhibitors of cell surface sialylation. Peracetylated 2-acetylamino-2-deoxy-3-O-methyl-d-mannose decreases cell surface sialylation in Jurkat cells in a dose-dependent manner up to 80%, quantified by flow cytometry and enzyme-linked lectin assays. High-performance liquid chromatography experiments revealed that not only the concentration of membrane bound but also of cytosolic sialic acid is reduced in treated cells. We have strong evidence that the observed reduction of sialic acid expression in cells is caused by the inhibition of the bifunctional enzyme UDP-GlcNAc-2-epimerase/ManNAc kinase. 2-Acetylamino-2-deoxy-3-O-methyl-d-mannose inhibits the human ManNAc kinase domain of the UDP-GlcNAc-2-epimerase/ManNAc kinase. Binding kinetics of the inhibitor and human N-acetylmannosamine kinase were evaluated using surface plasmon resonance. Specificity studies with human N-acetylglucosamine kinase and hexokinase IV indicated a high specificity of 2-acetylamino-2-deoxy-3-O-methyl-d-mannose for MNK. This substance represents a novel class of inhibitors of sialic acid expression in cells, targeting the key enzyme of sialic acid de novo biosynthesis.