FT-IR光谱法研究TA9902抑制Aβ_(1-42)聚集的分子机制  

Inhibitory effect of TA9902 on amyloid β-peptide 1-42 aggregation by Fourier-transform infrared spectroscopy study

作　　者：李光武[1] 汪华侨[1] 姚志彬[1] 

机构地区：[1]中山大学医学院解剖系脑研究室

出　　处：《中国病理生理杂志》2006年第1期84-87,共4页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30470904);广东省科技重点攻关项目(No.2KMO4106s);广东省自然科学基金资助项目(No.010698)

摘　　要：目的:研究TA9902引起Aβ1-42二级结构变化,了解其抑制Aβ聚集和纤维形成的机制。方法:用傅里叶变换红外光谱法(FT-IR)曲线拟合定量分析和特征频谱分析Aβ老化后及TA9902干预后二级结构的变化。结果:1700-1600cm-1之间的酰胺I带分析,Aβ1-42单独孵育30min时,β-折叠片为46.53%;Aβ1-42老化72h,β-折叠片为65.13%,β-折叠片增加了19.4%。TA9902与Aβ1-42作用β-折叠片为29.04%;与Aβ1-42老化72h相比,TA9902的存在明显减少β折叠片的含量(下降了36.09%),β-转角的含量明显升高(升高57.56%),α-螺旋也略有升高(2.93%)。呈现出明显的β折叠片向β-转角的转化。其它基团特征峰位显示,TA9902中有酮类尤其是饱和链状酮或α-二酮和烷烃类的-CH2和-CH参与了Aβ1-42的分子变构。结论:TA9902明显抑制Aβ1-42β-折叠的形成,同时也使Aβ1-42肽的侧链基团发生了化学修饰,提示Aβ的聚集和纤维形成与其分子β-折叠的形成和侧链基团发生了化学修饰有关。AIM： To investigate the mechanism by which TA9902 inhibits the formation of amyloid β- peptide （Aβ） fibrils. METHODS： Fourier- transform infrared spectroscopy was used to study the secondary structure changes on aging Aβ in vitro. RESULTS： The content of β- pleated sheet were 46.53% in the condition of Aβ aged alone for 30 min. When Aβ aged alone for 72 h, the content of β - pleated sheet increased about 19.4% and produced a shift of random coil toward β- pleated sheet. TA9902 induced a significant decrease in the content of β- pleated sheet （36.09%）. CONCLUSION： TA9902 effectively diminishes the β - pleated structural content. The effect of TA9902 on the secondary structure of aged Aβ is associated with inhibition of Aβ aggregation and fibril formation.

关 键 词：阿尔茨海默病 淀粉样Β蛋白 傅里叶变换红外 光谱法 分子机制 

分 类 号：R363[医药卫生—病理学]