首页> 外文期刊>Chemistry: A European journal >Inhibiting and Reversing Amyloid-β Peptide (1–40) Fibril Formation with Gramicidin S and Engineered Analogues
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Inhibiting and Reversing Amyloid-β Peptide (1–40) Fibril Formation with Gramicidin S and Engineered Analogues

机译:用葛米素S和工程类似物抑制和逆转淀粉样β肽(1-40)的原纤维形成。

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摘要

In Alzheimer's disease, amyloid- β (Aβ) peptides aggregate into extracellular fibrillar deposits. Although these deposits may not be the prime cause of the neurodegeneration that characterizes this disease, inhibition or dissolution of amyloid fibril formation by Aβ peptides is likely to affect its development. ThT fluorescence measurements and AFM images showed that the natural antibiotic gramicidin S significantly inhibited Ab amyloid formation in vitro and could dissolve amyloids that had formed in the absence of the antibiotic. In silico docking suggested that gramicidin S, a cyclic decapeptide that adopts a β-sheet conformation, binds to the Aβ peptide hairpinstacked fibril through β-sheet interactions. This may explain why gramicidin S reduces fibril formation. Analogues of gramicidin S were also tested. An analogue with a potency that was four-times higher than that of the natural product was identified.
机译:在阿尔茨海默氏病中,淀粉样β(Aβ)肽聚集到细胞外纤维状沉积物中。尽管这些沉积物可能不是该疾病特征性神经变性的主要原因,但Aβ肽对淀粉样蛋白原纤维形成的抑制或溶解可能会影响其发展。 ThT荧光测量和AFM图像显示,天然抗生素短杆菌肽S在体外显着抑制Ab淀粉样蛋白的形成,并且可以溶解在不存在抗生素的情况下形成的淀粉样蛋白。在计算机对接中表明,短杆菌肽S(一种采取β-折叠构象的环状十肽)通过β-折叠相互作用与Aβ肽发夹堆叠的原纤维结合。这可以解释为什么短杆菌肽S减少原纤维形成。还测试了短杆菌肽S的类似物。鉴定出一种效力比天然产物高四倍的类似物。

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