Hydroxylated single-walled carbon nanotube inhibits β2m21-31 fibrillization and disrupts pre-formed proto-fibrils.
Hydroxylated single-walled carbon nanotube inhibits β2m21-31 fibrillization and disrupts pre-formed proto-fibrils.
复制标题
羟基化单壁碳纳米管抑制β2m21-31 原纤维化并破坏预先形成的原纤维。
DOI：
10.1016/j.ijbiomac.2021.10.103
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发表时间：
2021-10
影响因子：
8.2
通讯作者：
Yunxiang Sun
中科院分区：
文献类型：
--
作者：
Yu Zhang;Yuying Liu;Wenhui Zhao;Yunxiang Sun
淀粉样多肽的病理性聚集与许多退行性疾病相关。防止聚集和清除淀粉样蛋白沉积被认为是对抗淀粉样变性的有希望的策略。羟基化单壁碳纳米管（SWCNT-OH）具有良好的生物相容性和良好的血脑屏障穿透能力，具有良好的抗淀粉样蛋白活性。本文采用全原子离散分子动力学（DMD）模拟方法，系统研究了SWCNT-OH对β 2 m21 - 31多肽纤维化的影响。我们的研究结果表明，分离的β 2 m21 - 31肽首先成核为非结构化的寡聚体，然后在至少有六个肽的寡聚体中进行卷曲到折叠构象转换。预形成的β-折叠的伸长和侧表面可以催化其他非结构化单体和小的寡聚物通过对接锁原纤维生长和二次成核过程转化为β-折叠形成。最终，β 2 m21 - 31肽将自组装成有序的交叉β结构。无论是单分子还是交叉β组装体，β 2 m21 - 31均以非结构化形式附着在SWCNT-OH表面，表明SWCNT-OH不仅抑制了β 2 m21 - 31的纤维化，而且破坏了预形成的原纤维。总之，我们的研究揭示了β 2 m21 - 31的纤维化机制和SWCNT-OH的淀粉样蛋白抑制机制，为抗淀粉样蛋白抑制剂的从头设计提供了新的思路。
Pathological aggregation of amyloid polypeptides is associated with numerous degenerative diseases. Preventing aggregation and clearing amyloid deposits are considered as promising strategies against amyloidosis. With the capacity of crossing the blood-brain barrier and good biocompatibility, the hydroxylated single-walled carbon nanotube (SWCNT-OH) has been shown with excellent anti-amyloid properties. Here, we systematically studied the SWCNT-OH effects on the fibrillization of the β2m21–31peptides utilizing all-atom discrete molecular dynamics (DMD) simulation. Our results demonstrated the isolated β2m21–31peptides first nucleated into unstructured oligomers followed by coil-to-sheet conformational conversions in oligomers with at least six peptides. The elongation and lateral surfaces of the preformed β-sheet could catalyze the other unstructured monomers and small oligomers converted into β-sheet formations via dock-lock fibril growth and secondary nucleation processes. Eventually, the β2m21–31peptides would self-assemble into well-ordered cross-β structures. Regardless of isolated monomers or well-defined cross-β assemblies, the β2m21–31would attach on the surfaces of SWCNT-OH adopting unstructured formations indicating the SWCNT-OH not only inhibited the fibrillization of β2m21–31but also destroyed pre-formed proto-fibrils. Overall, our study displays a complete picture of the fibrillization mechanism of β2m21–31and the amyloid inhibitory mechanism of SWCNT-OH, offering new insight into the de-novo design of anti-amyloid inhibitors.
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DOI：
10.1073/pnas.ss11136
发表时间：
2014-09
期刊：
Proceedings of the National Academy of Sciences
影响因子：
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作者：
通讯作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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DOI：
10.1016/j.ijbiomac.2021.07.056
发表时间：
2021-07
影响因子：
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DOI：
10.1016/j.bbadis.2018.11.021
发表时间：
2019-02-01
期刊：
Biochimica et biophysica acta. Molecular basis of disease
影响因子：
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作者：
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影响因子：
4.8
作者：
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