手性(物理)
纳米尺度
圆二色性
分子动力学
纤颤
材料科学
动力学
化学
纳米技术
结晶学
计算化学
手征对称性
物理
心房颤动
医学
量子力学
Nambu–Jona Lasinio模型
心脏病学
夸克
作者
Guanbin Gao,Guowei Zhu,Liangchong Yu,Zijun Zhang,Ting Zhang,Xinglin Liu,Cheng Zhang,Ling Zhou,Taolei Sun
出处
期刊:Nano Research
[Springer Nature]
日期:2022-04-28
卷期号:15 (7): 6721-6729
被引量:5
标识
DOI:10.1007/s12274-022-4303-9
摘要
β-Amyloid (Aβ) peptide fibrillation, one of the characteristic hallmarks of Alzheimer’s disease, is determined by many interfacial physical-chemical factors, e.g., charge, hydrophobicity, etc. Despite extensive research, chiral effect in different-scales on the fibrillation process of Aβ remains unclear. Herein, molecular-scale, sub-nanoscale, and nanoscale chiral-structures were constructed to investigate their chiral effect on the fibrillation of Aβ40 peptides. Chiral structures from molecular-scale to nanoscale were obtained from the different periods of the chemosynthesis process of chiral ZnS quantum-dots (QDs), confirmed by real-time monitoring of circular dichroism spectra. For molecular-scale, both L-penicillamine (L-P) and D-P ligands accelerated the fibrillation of Aβ40, and the speed-up effect of D-P was slightly stronger than L-P. For sub-nanoscale, both two chiral Zn-complexes (L-Zn and D-Zn) induced the agglomeration of Aβ40 without chirality discrimination. For nanoscale, both L-ZnS and D-ZnS QDs inhibited the fibrillation of Aβ40, and the inhibition effect of L-ZnS was notably better than that of D-ZnS. In-situ kinetics experiments of Aβ40 co-incubated with two chiral QDs demonstrated that L-ZnS completely prevents the misfolding of Aβ40 from unfolded to β-sheet, while D-ZnS cannot achieve this. Further site-replacement experiments and simulation results revealed the underlying molecular mechanisms of the different inhibition efficiency of chiral ZnS QDs on Aβ40 fibrillation, which mainly attribute to the stereoselectivity interaction between the chiral ligands of ZnS QDs and electro-positive amino acid residues (R5, K16, and K28) of Aβ40. This work offers a microscopic insight of chiral effect on Aβ fibrillation exerted by structures in different-scales, and provides a guidance in precise regulation of protein fibrillation via manipulating chiral structures in different-scales.
科研通智能强力驱动
Strongly Powered by AbleSci AI