阿尔茨海默氏症致病蛋白-Aβ_((12-28))肽段的NMR研究

摘要

Oligomerization of Aβ peptides and fibril formation play critical roles in the pathology of Alzheimer's disease (AD). Aβ_((1-42)) is the most toxic species of the Aβ peptides. Disruption of Aβ aggregation is a promising approach in developing therapeutics for AD. In our previous studies, some compounds were found to be able to bind to Aβ_((12-28)). In this work, two-dimensional NMR methods were used to assign the ~1H and ~(15)N chemical shifts of Aβ_((12-28)) peptide. The results should provide a basis for the interaction study of Aβ_((12-28)) peptide with small molecule inhibitors.%Aβ肽的多聚化和纤维化在阿尔茨海默氏症(Alzheimer's diseas)的发生中起关键作用, 其中以Aβ_((1-42))的致病作用为最强,因此阻断其聚集成为阿尔茨海默氏症一种潜在的治疗方式. 作者在研究中发现某些化合物可以结合于Aβ_((12-28))肽段. 该文采用~1H-~1H COSY、 TOCSY、 ROESY和~(15)N-HSQC多种核磁分析方法, 对此肽段的~1H和~(15)N NMR谱信号进行了归属和详细分析, 为进一步研究其与小分子抑制剂的相互作用提供了基础.