本文選題：熒光探針 + 谷胱甘肽　； 參考：《延邊大學(xué)》2017年博士論文

【摘要】：細胞內(nèi)的谷胱甘肽(GSH)是含量最多的非蛋白生物硫醇,濃度在1-10mM之間,通過還原型GSH與氧化型GSSG維持細胞內(nèi)的氧化還原平衡。因此,實時檢測GSH的濃度,有助于了解細胞內(nèi)的氧化還原態(tài)的變化。目前開發(fā)的熒光探針只能對GSH定性,不能進行定量或者濃度的動態(tài)檢測�；诖�,本研究設(shè)計合成了一類基于α,β-不飽和酮可逆加成機理的新型比率熒光探針,可視化研究了體外和細胞內(nèi)GSH含量的變化,實現(xiàn)了在分子和細胞層次上對GSH原位、實時、動態(tài)熒光成像分析。通過對結(jié)構(gòu)的優(yōu)化,調(diào)控了探針與GSH的反應(yīng)活性。其中,氰基丙烯酰胺類化合物4d與GSH發(fā)生可逆加成反應(yīng),解離常數(shù)為2.59mM,利用該探針定量了 Hela細胞內(nèi)GSH(5.40±0.87mM)。氰基丙烯酸酯類化合物4c可以特異性的識別亞硫酸氫根,是一種利用率極高的可再生性熒光探針,利用該探針對亞硫酸鹽的熒光檢測,可以全程跟蹤亞硫酸鹽引發(fā)的疾病狀態(tài)以及治療過程,對了解發(fā)病的途徑和治療的效果帶來巨大的幫助。將齊墩果酸與可逆性GSH熒光探針相偶聯(lián),熒光成像研究揭示了齊墩果酸作用過程中GSH的實時變化,有助于研究GSH與藥效、細胞凋亡之間的聯(lián)系。將齊墩果酸與指示型熒光團相連,利用熒光的性能觀察了藥物在細胞內(nèi)的特異性定位和藥物刺激后細胞內(nèi)的應(yīng)激變化。本文主要探索了可逆熒光探針定量以及實時檢測GSH的問題,同時將其與藥物偶聯(lián),利用藥物的抗癌活性和探針的定位、識別能力,探索了藥物的作用機理。
[Abstract]:Intracellular glutathione glutathione (GSH) is the most abundant non-protein biological mercaptan. The concentration of glutathione is between 1-10mM and redox equilibrium is maintained by reductive GSH and oxidized GSSG. Therefore, real-time detection of GSH concentration is helpful to understand the changes of redox state in cells. The fluorescence probe developed at present can only determine GSH qualitatively, but not quantitatively or dynamically. Based on this, a novel fluorescent probe based on the reversible addition mechanism of 偽, 尾 -unsaturated ketones was designed and synthesized. The changes of GSH content in vitro and in cells were visualized, and the GSH in situ and in real time were realized at molecular and cellular levels. Dynamic fluorescence imaging analysis. The reactivity of the probe and GSH was regulated by optimizing the structure of the probe. The cyanoacrylamide compounds reacted with GSH for 4 d and the dissociation constant was 2.59mM.The probe was used to quantify GSH(5.40 鹵0.87mM-1 in Hela cells. Cyanoacrylates (4c) can specifically recognize hydrogen sulfite, which is a highly efficient renewable fluorescent probe for the fluorescence detection of sulfites. It can be used to track the state of the sulfite-induced disease and the course of treatment all the time. It is helpful to understand the way of the disease and the effect of treatment. By coupling oleanolic acid with reversible GSH fluorescence probe, fluorescence imaging revealed the real time change of GSH during the process of oleanolic acid action, which was helpful to study the relationship between GSH and pharmacodynamics and apoptosis. Oleanolic acid was linked to the indicative fluorescence group. The specific localization of the drug in the cells and the changes of the intracellular stress after stimulation were observed by using the fluorescence properties. In this paper, the quantitative and real-time detection of GSH with reversible fluorescence probe was studied. At the same time, the mechanism of drug action was explored by using the anti-cancer activity of the drug and the location of the probe, as well as the recognition ability of the probe.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R91;O657.3

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