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Chemical and Physical Variability in Structural Isomers of an L/D alpha-Sheet Peptide Designed To Inhibit Amyloidogenesis

机译:L / Dα-板肽的结构异构体中的化学和物理变异,旨在抑制淀粉样蛋白发生

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摘要

There has been much interest in synthetic peptides as inhibitors of aggregation associated with amyloid diseases. Of particular interest are compounds that target the cytotoxic soluble oligomers preceding the formation of mature, nontoxic fibrils. This study explores physical and chemical differences between two de novo-designed peptides that share an identical primary structure but differ in backbone chirality at six key positions. We show that the presence of alternating L/D-amino acid motifs dramatically increases aqueous solubility, enforces alpha-sheet secondary structure, and inhibits aggregation of the beta-amyloid peptide implicated in Alzheimer's disease, in addition to neutralizing its cytotoxicity. In contrast, the all-L-amino acid isomer does not form alpha-sheet structure and is insoluble and inactive.
机译:对合成肽的兴趣很多,作为与淀粉样疾病相关的聚集抑制剂。 特别令人兴趣的是靶向成熟,无毒原纤维形成前面的细胞毒性可溶性低聚物的化合物。 本研究探讨了在六个关键位置的相同主要结构的两种设计肽之间的物理和化学差异,但在六个关键位置不同。 我们表明,交替的L / D-氨基酸基序的存在显着增加了含水溶解度,实施α-薄片二次结构,并抑制β-淀粉样肽的聚集,除了中和其细胞毒性之外。 相反,全-1-氨基酸异构体不形成α-片状结构并且不溶于和无活性。

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  • 来源
    《Biochemistry》 |2018年第5期|共4页
  • 作者单位

    Univ Washington Dept Bioengn Box 355013 Seattle WA 98195 USA;

    Univ Washington Dept Mol Engn Box 355013 Seattle WA 98195 USA;

    Univ Washington Dept Bioengn Box 355013 Seattle WA 98195 USA;

    Univ Washington Dept Bioengn Box 355013 Seattle WA 98195 USA;

    Univ Washington Dept Bioengn Box 355013 Seattle WA 98195 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

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