N-benzyloxycarbonyl-3-O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-L-threonine tert-butyl ester | 1245797-75-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-benzyloxycarbonyl-3-O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-L-threonine tert-butyl ester
• CAS: 1245797-75-4
• 化学式: C₄₃H₅₁NO₉
• 分子量: 725.879
• InChiKey: JLLUBOPDQPPMPH-ITZCYCLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.53
• 重原子数：
  53.0
• 可旋转键数：
  16.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  110.78
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  N-benzyloxycarbonyl-3-O-trimethylsilyl-L-threonine tert-butyl ester 、 2,3,4-三-O-苄基-L-吡喃岩藻糖基氟化物 在 三氟化硼乙醚 作用下， 以 乙醚 为溶剂， 反应 2.0h， 生成 N-benzyloxycarbonyl-3-O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-L-threonine tert-butyl ester 、 N-benzyloxycarbonyl-3-O-(2,3,4-tri-O-benzyl-β-L-fucopyranosyl)-L-threonine tert-butyl ester
  参考文献：
  名称：

  Chemical Synthesis, Folding, and Structural Insights into O-Fucosylated Epidermal Growth Factor-like Repeat 12 of Mouse Notch-1 Receptor

  摘要：

  Notch receptors are cell surface glycoproteins that play key roles in a number of developmental cascades in metazoa. The extracellular domains of Notch-1 receptors are composed of 36 tandem epidermal growth factor (EGF)-like repeats, many of which are modified at highly conserved consensus sites by an unusual form of O-glycan, with O-fucose. The O-fucose residues on certain EGF repeats may be elongated. In mammalian cells this can be a tetrasaccharide, Siaα2,3Galβ1,4GlcNAcβ1,3Fucα1→. This elongation process is initiated by the action of O-fucose-specific β1,3 N-acetylglucosaminyltransferases of the Fringe family. There is evidence that the addition of GlcNAc by Fringe serves as an essential modulator of the interaction of Notch with its ligands and the triggering of activation. Here we describe the efficient synthesis, folding, and structural characterization of EGF repeat 12 (EGF 12) of a mouse Notch-1 receptor bearing different O-fucose glycan chains. We demonstrate that the three disulfide bonds, Cys(456)-Cys(467) (C1-C3), Cys(461)-Cys(476) (C2-C4), and Cys(478)-Cys(487) (C5-C6) were correctly formed in the nonglycosylated as well as the O-fucosylated forms of EGF 12. Three-dimensional structural studies by NMR reveal that the methyl group of fucose is in close contact with ILe(475), Met(477), Pro(478) residues and this stabilizes the conformation of the antiparallel β-sheet of EGF 12. The addition of the GlcNAc residue on O-fucosylated EGF 12 induces a significant conformational change in the adjacent tripeptide sequence, Gln(462)Asn(463)Asp(464), which is a motif involved in the natural, enzymatic O-fucosylation at the conserved site (Cys(461)X(4)Ser/ThrCys(467)).

  DOI：

  10.1021/ja105216u