【摘要】：熒光染料硫黃素T常用于淀粉樣纖維聚集過程的定性定量檢測。雖然有研究表明,某些抑制淀粉樣蛋白質(zhì)聚集的小分子抑制劑會與硫黃素T相互作用,影響其測試結(jié)果。但硫黃素T如何影響淀粉樣蛋白質(zhì)的聚集成核動力學(xué)尚不清晰。本文以淀粉樣β-蛋白質(zhì)40(Aβ40)為模型,系統(tǒng)研究了硫黃素T對Aβ40聚集成核的影響。研究發(fā)現(xiàn):硫黃素T能夠顯著改變Aβ40的聚集成核動力學(xué),且影響程度與硫黃素T的濃度密切相關(guān)。即在低濃度硫黃素T存在下,Aβ40成核速率的延遲時間先隨著硫黃素T濃度的升高而縮短,后隨著硫黃素T濃度的升高延遲時間反而延長。但延伸的速率卻隨硫黃素T濃度的升高而緩慢增大。另外,硫黃素T基本不會影響Aβ40的二級結(jié)構(gòu)和纖維形態(tài)。同時,等溫滴定微量熱實驗結(jié)果表明,硫黃素T結(jié)合Aβ40之間的主要作用力為疏水相互作用。據(jù)此,本研究提出硫黃素T對Aβ40聚集成核動力學(xué)的雙重影響機理。這些結(jié)果有助于進一步了解硫黃素T與淀粉樣蛋白質(zhì)的作用特點,為今后硫黃素T在Aβ40聚集成核動力學(xué)實驗中的使用提供參考。
[Abstract]:Fluorescence dye thioflavone T is often used for qualitative and quantitative determination of amyloid fiber aggregation process. Although studies have shown that some small molecular inhibitors that inhibit the aggregation of amyloid proteins interact with thiocyanin T to influence their test results. However, it is not clear how sulfur T affects the aggregation of amyloid proteins into nuclear power. Using amyloid 尾 -protein 40 (A 尾 40) as a model, the effects of thiocyanin T on the aggregation and nucleation of A 尾 40 were studied systematically. It was found that thiocyanin T could significantly change the aggregation of A 尾 40 into nuclear power science, and the degree of influence was closely related to the concentration of thiocyanin T. In the presence of low concentration of thiocyanin T, the delay time of A 尾 40 nucleation rate was first shortened with the increase of S T concentration, and then prolonged with the increase of S T concentration. However, the rate of extension increased slowly with the increase of sulfur T concentration. In addition, thiocyanin T had little effect on the secondary structure and fiber morphology of A 尾 40. At the same time, the results of isothermal titration showed that hydrophobic interaction was the main force between thiocyanin T and A 尾 40. Based on this, the mechanism of the double effect of sulfur T on the aggregation of A 尾 40 into nuclear power is proposed. These results are helpful to further understand the interaction between thiocyanin T and amyloid protein, and provide a reference for the application of thiocyanin T in A 尾 40 aggregation nuclear power experiment in the future.
【作者單位】： 天津大學(xué)化工學(xué)院生物工程系系統(tǒng)生物工程教育部重點實驗室;
【基金】：supported by the National Natural Science Foundation of China(21236005,21376172,21406160,21576199)~~
【分類號】：O641.3
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本文編號：2302125