Diac-(Val-Thr(bzl)-Val-Thr(bzl)-dmda)2 | 287957-61-3

• 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: Diac-(Val-Thr(bzl)-Val-Thr(bzl)-dmda)2
• CAS: 287957-61-3
• 化学式: C₉₀H₁₂₄N₁₂O₁₅
• 分子量: 1614.05
• InChiKey: XOXYVQLLBRGRAS-VBUUYKOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.73
• 重原子数：
  117.0
• 可旋转键数：
  48.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  347.54
• 氢给体数：
  10.0
• 氢受体数：
  17.0

反应信息

• 作为反应物：
  描述：

  Diac-(Val-Thr(bzl)-Val-Thr(bzl)-dmda)2 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 Diac-(Val-Thr-Val-Thr-dmda)2
  参考文献：
  名称：

  Controlling the Morphology of Cross β-Sheet Assemblies by Rational Design

  摘要：

  Low molecular weight peptidomimetics with simple amphiphilic sequences can help to elucidate the structures of cross beta-sheet assemblies, such as amyloid fibrils. The peptidomimetics described herein comprise a dibenzofuran template, two peptide strands made up of alternating hydrophilic and hydrophobic residues, and carboxyl termini, each of which can be varied to probe the structural requirements for beta-sheet self-assembly processes. The dibenzofuran template positions the strands approximately 10 angstrom apart, allowing corresponding hydrophobic side chains in the strands to pack into a collapsed U-shaped structure. This conformation is stabilized by hydrophobic interactions, not intramolecular hydrogen bonds. Intermolecular stacking of the collapsed peptidomimetics, enabled by intermolecular hydrogen bonding and hydrophobic interactions, affords 25-27 angstrom wide protofilaments having a cross beta-sheet structure. Association of protofilaments, mediated by the dibenzofuran substructures and driven by the hydrophobic effect, affords 50-60 angstrom wide filaments. These widths can be controlled by changing the length of the peptide strands. Further assembly of the filaments into fibrils or ribbons can be controlled by modification of the template, C-terminus, and buffer ion composition.

  DOI：

  10.1021/ja050558c
• 作为产物：
  描述：

  2,8-dibenzofuranbis(3-propionic acid) 、 (S)-2-Amino-N-((1S,2R)-2-benzyloxy-1-{(S)-1-[(1S,2R)-2-benzyloxy-1-(2-dimethylamino-ethylcarbamoyl)-propylcarbamoyl]-2-methyl-propylcarbamoyl}-propyl)-3-methyl-butyramide 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 Diac-(Val-Thr(bzl)-Val-Thr(bzl)-dmda)2
  参考文献：
  名称：

  Controlling the Morphology of Cross β-Sheet Assemblies by Rational Design

  摘要：

  Low molecular weight peptidomimetics with simple amphiphilic sequences can help to elucidate the structures of cross beta-sheet assemblies, such as amyloid fibrils. The peptidomimetics described herein comprise a dibenzofuran template, two peptide strands made up of alternating hydrophilic and hydrophobic residues, and carboxyl termini, each of which can be varied to probe the structural requirements for beta-sheet self-assembly processes. The dibenzofuran template positions the strands approximately 10 angstrom apart, allowing corresponding hydrophobic side chains in the strands to pack into a collapsed U-shaped structure. This conformation is stabilized by hydrophobic interactions, not intramolecular hydrogen bonds. Intermolecular stacking of the collapsed peptidomimetics, enabled by intermolecular hydrogen bonding and hydrophobic interactions, affords 25-27 angstrom wide protofilaments having a cross beta-sheet structure. Association of protofilaments, mediated by the dibenzofuran substructures and driven by the hydrophobic effect, affords 50-60 angstrom wide filaments. These widths can be controlled by changing the length of the peptide strands. Further assembly of the filaments into fibrils or ribbons can be controlled by modification of the template, C-terminus, and buffer ion composition.

  DOI：

  10.1021/ja050558c

文献信息

• Protofilaments, Filaments, Ribbons, and Fibrils from Peptidomimetic Self-Assembly:  Implications for Amyloid Fibril Formation and Materials Science
  作者：Hilal A. Lashuel、Steven R. LaBrenz、Linda Woo、Louise C. Serpell、Jeffery W. Kelly

  DOI：10.1021/ja9937831

  日期：2000.6.1

  Deciphering the mechanism(s) of beta-sheet mediated self-assembly is essential for understanding amyloid fibril formation and for the fabrication of polypeptide materials. Herein, we report a simple peptidomimetic that self-assembles into polymorphic beta-sheet quaternary structures including protofilaments, filaments, fibrils, and ribbons that are reminiscent of the highly ordered structures displayed by the amyloidogenic peptides A beta, calcitonin, and amylin. The distribution of quaternary structures can be controlled by and in some cases specified by manipulating the pH, buffer composition, and the ionic strength. The ability to control beta-sheet-mediated assembly takes advantage of quaternary structure dependent pK(a) perturbations. Biophysical methods including analytical ultracentrifugation studies as well as far-UV circular dichroism and FT-IR spectroscopy demonstrate that linked secondary and quaternary structural changes mediate peptidomimetic self-assembly. Electron and atomic force microscopy reveal that peptidomimetic assembly involves numerous quaternary structural intermediates that appear to self-assemble in a convergent fashion affording quaternary structures of increasing complexity. The ability to control the assembly pathway(s) and the final quaternary structure(s) afforded should prove to be particularly useful in deciphering the quaternary structural requirements for amyloid fibril formation and for the construction of noncovalent macromolecular structures.