methyl (2S)-4-methyl-2-[[(2S)-3-methyl-2-[3-[[(2R,3R,4S,5R,6R)-6-[2-[[(2S)-3-methyl-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]butanoyl]amino]ethoxy]-3,4,5-tris(phenylmethoxy)oxan-2-yl]methoxy]propanoylamino]butanoyl]amino]pentanoate | 1351945-91-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2S)-4-methyl-2-[[(2S)-3-methyl-2-[3-[[(2R,3R,4S,5R,6R)-6-[2-[[(2S)-3-methyl-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]butanoyl]amino]ethoxy]-3,4,5-tris(phenylmethoxy)oxan-2-yl]methoxy]propanoylamino]butanoyl]amino]pentanoate
• CAS: 1351945-91-9
• 化学式: C₅₇H₈₃N₅O₁₄
• 分子量: 1062.31
• InChiKey: BDMVJTJGNDYKIC-CJMQILBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  76
• 可旋转键数：
  33
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  236
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  methyl (2S)-4-methyl-2-[[(2S)-3-methyl-2-[3-[[(2R,3R,4S,5R,6R)-6-[2-[[(2S)-3-methyl-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]butanoyl]amino]ethoxy]-3,4,5-tris(phenylmethoxy)oxan-2-yl]methoxy]propanoylamino]butanoyl]amino]pentanoate 在 氢气 、 palladium(II) hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 以96%的产率得到methyl (2S)-4-methyl-2-[[(2S)-3-methyl-2-[3-[[(2R,3S,4S,5R,6R)-3,4,5-trihydroxy-6-[2-[[(2S)-3-methyl-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]butanoyl]amino]ethoxy]oxan-2-yl]methoxy]propanoylamino]butanoyl]amino]pentanoate
  参考文献：
  名称：

  Sugar-based peptidomimetics inhibit amyloid β-peptide aggregation

  摘要：

  Alzheimer's disease is characterized by the oligomerization and amyloid fibril formation of amyloid beta-peptide (A beta). We describe a novel class of small water-soluble A beta binding peptidomimetics based on two hydrophobic Ala-Val and Val-Leu dipeptides linked to a D-glucopyranosyl scaffold through aminoalkyl and carboxyethyl links in C1 and C6 positions. These compounds combine the targeting of hydrophobic recognition interfaces with an original hydrophilic sugar beta-breakage strategy. These molecules were shown, by fluorescence thioflavin-T assays, to dramatically slow down the kinetics of amyloid fibril formation even at a low peptidomimetics to A beta ratio of 0.1:1. Electron microscopy images revealed that the peptidomimetics efficiently reduced the amount of typical amyloid fibrils. NMR saturation transfer difference experiments indicated that these molecules interact with A beta aggregated species through their hydrophobic amino acid residues. This inhibition effect was found to be sequence-specific since these molecules did not alter the kinetics of aggregation of another amyloid peptide, IAPP, involved in type 2 diabetes mellitus. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.008
• 作为产物：
  描述：

  methyl (3-(((2R,3R,4S,5R)-6-(2-aminoethoxy)-3,4,5-tris(benzyloxy)tetrahydro-2H-pyran-2-yl)methoxy)propanoyl)-L-valyl-L-leucinate 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 90.0h， 生成 methyl (2S)-4-methyl-2-[[(2S)-3-methyl-2-[3-[[(2R,3R,4S,5R,6R)-6-[2-[[(2S)-3-methyl-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]butanoyl]amino]ethoxy]-3,4,5-tris(phenylmethoxy)oxan-2-yl]methoxy]propanoylamino]butanoyl]amino]pentanoate
  参考文献：
  名称：

  Sugar-based peptidomimetics inhibit amyloid β-peptide aggregation

  摘要：

  Alzheimer's disease is characterized by the oligomerization and amyloid fibril formation of amyloid beta-peptide (A beta). We describe a novel class of small water-soluble A beta binding peptidomimetics based on two hydrophobic Ala-Val and Val-Leu dipeptides linked to a D-glucopyranosyl scaffold through aminoalkyl and carboxyethyl links in C1 and C6 positions. These compounds combine the targeting of hydrophobic recognition interfaces with an original hydrophilic sugar beta-breakage strategy. These molecules were shown, by fluorescence thioflavin-T assays, to dramatically slow down the kinetics of amyloid fibril formation even at a low peptidomimetics to A beta ratio of 0.1:1. Electron microscopy images revealed that the peptidomimetics efficiently reduced the amount of typical amyloid fibrils. NMR saturation transfer difference experiments indicated that these molecules interact with A beta aggregated species through their hydrophobic amino acid residues. This inhibition effect was found to be sequence-specific since these molecules did not alter the kinetics of aggregation of another amyloid peptide, IAPP, involved in type 2 diabetes mellitus. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.008

文献信息

• Sugar-based peptidomimetics inhibit amyloid β-peptide aggregation
  作者：Bertrand Dorgeret、Lucie Khemtémourian、Isabelle Correia、Jean-Louis Soulier、Olivier Lequin、Sandrine Ongeri

  DOI：10.1016/j.ejmech.2011.10.008

  日期：2011.12

  Alzheimer's disease is characterized by the oligomerization and amyloid fibril formation of amyloid beta-peptide (A beta). We describe a novel class of small water-soluble A beta binding peptidomimetics based on two hydrophobic Ala-Val and Val-Leu dipeptides linked to a D-glucopyranosyl scaffold through aminoalkyl and carboxyethyl links in C1 and C6 positions. These compounds combine the targeting of hydrophobic recognition interfaces with an original hydrophilic sugar beta-breakage strategy. These molecules were shown, by fluorescence thioflavin-T assays, to dramatically slow down the kinetics of amyloid fibril formation even at a low peptidomimetics to A beta ratio of 0.1:1. Electron microscopy images revealed that the peptidomimetics efficiently reduced the amount of typical amyloid fibrils. NMR saturation transfer difference experiments indicated that these molecules interact with A beta aggregated species through their hydrophobic amino acid residues. This inhibition effect was found to be sequence-specific since these molecules did not alter the kinetics of aggregation of another amyloid peptide, IAPP, involved in type 2 diabetes mellitus. (C) 2011 Elsevier Masson SAS. All rights reserved.