本文選題：hIAPP20-29 + 胰島淀粉樣多肽聚集　； 參考：《江蘇大學(xué)》2017年碩士論文

【摘要】：淀粉樣多肽的錯誤折疊與多種退行性疾病的致病機制密切相關(guān),例如:阿茲海默氏病、帕金森病、II-型糖尿病、亨廷頓病。而其中,II-型糖尿病,也被稱作非胰島素依賴型糖尿病,是糖尿病最常見方式的一種,約占患者人數(shù)的90%以上。找到糖尿病的有效治療或者控制方法是目前急需解決的重要問題。胰島淀粉樣多肽是一段包含有37個氨基酸殘基的多肽鏈,研究表明,其形成的淀粉樣在胰島的沉積與II-型糖尿病的發(fā)病有著密不可分的聯(lián)系。H2NSNNFGILSS-COOH(hIAPP20-29)是胰島淀粉樣多肽成纖維的核心片段,因此研究如何調(diào)控這段十個氨基酸的短肽序列的聚集,對于尋找有效治療II-型糖尿病的方法具有重要的指導(dǎo)意義。在本文中,我們利用光驅(qū)動卟啉分子成功地抑制了hIAPP20-29的自聚集以及降解了其自聚集形成的淀粉樣纖維。并結(jié)合DCF熒光、PeakForce Quantitative Nanoscale Mechanical和UV光譜對其調(diào)控機理進(jìn)行了合理的推測。這一發(fā)現(xiàn)對以后設(shè)計新的調(diào)控胰島淀粉樣多肽聚集的方法提供了一定的指導(dǎo)意義,同時也豐富了抑制劑的選擇。具體的研究內(nèi)容如下:(1)我們利用圓二色譜(circular dichroism,CD)、Thioflavin T熒光標(biāo)記以及原子力顯微鏡(AFM)技術(shù),對hIAPP20-29自聚集的過程,二級結(jié)構(gòu)的變化,以及聚集體形貌演變進(jìn)行了表征分析。(2)系統(tǒng)的研究了光照、卟啉分子、光驅(qū)動卟啉分子以及其濃度變化對于調(diào)控胰島淀粉樣多肽聚集形貌及其力學(xué)性質(zhì)的影響。結(jié)果表明光驅(qū)動卟啉分子可以有效地抑制hIAPP20-29的聚集,其形貌以及二級結(jié)構(gòu)的變化受卟啉分子濃度的影響,發(fā)生從短纖維到膜狀結(jié)構(gòu)和β-折疊到無規(guī)卷曲的轉(zhuǎn)變。其結(jié)構(gòu)的楊氏模量隨著卟啉分子濃度的提高逐漸增強,說明卟啉參與了多肽的自組裝過程。Dichlorofluorescein光譜以及UV光譜測試表明了光刺激條件下的卟啉分子產(chǎn)生的ROS破壞了多肽鏈之間氫鍵的相互作用,從而破壞了原有的自組裝過程,而且光驅(qū)動卟啉分子抑制效果在無持續(xù)光照刺激下具有持續(xù)抑制作用。(3)利用光驅(qū)動卟啉分子進(jìn)一步的降解了成熟的淀粉樣多肽纖維表明光驅(qū)動卟啉分子具有降解成熟纖維的效果。
[Abstract]:Misfolding of amyloid peptides is closely related to the pathogenesis of a variety of degenerative diseases, such as Aziz Heimo S's, Parkinson's, type II-, and Huntington's disease. Among them, type II- diabetes, also known as non insulin dependent diabetes, is one of the most common ways of diabetes, accounting for about 90% of the number of patients. To find diabetes. The effective treatment or control method of disease is an important problem to be solved urgently. Islet amyloid polypeptide is a polypeptide chain containing 37 amino acid residues. The study shows that the deposition of amyloid in the islets of the pancreas is inextricably linked to the onset of type II- diabetes.H2NSNNFGILSS-COOH (hIAPP20-29) is the amyloid islet like It is important to study how to regulate the aggregation of short peptide sequences of the ten amino acids, which is of great significance for the search for the effective treatment of II- type diabetes. In this paper, we successfully inhibit the self aggregation of hIAPP20-29 and degrade its self aggregation by using light driven porphyrin molecules. The regulatory mechanism of the amyloid fibers, combined with DCF fluorescence, PeakForce Quantitative Nanoscale Mechanical and UV spectra, has been reasonably speculated. This discovery provides a certain guiding significance for the design of a new method of regulating the aggregation of islet amyloid peptides in the future, and is also rich in the selection of the inhibitors. (1) (1) we used circular two chromatography (circular dichroism, CD), Thioflavin T fluorescence labeling and atomic force microscopy (AFM) to characterize the self aggregation of hIAPP20-29, the changes in the two structure and the evolution of the aggregate morphology. (2) the system has studied the illumination, porphyrin, light driven porphyrin and its concentration change. The effects on the morphology and mechanical properties of the islet amyloid peptides are regulated. The results show that the porphyrin molecules can effectively inhibit the aggregation of hIAPP20-29. The changes of the morphology and the structure of the two stage are influenced by the molecular concentration of porphyrin, and the structure of the transition from short fiber to membranous structure and beta fold to random curl. The young's modulus increases with the increase of the molecular concentration of porphyrin, indicating that porphyrin participates in the.Dichlorofluorescein spectrum of the self-assembly process of the polypeptide and the UV spectrum test shows that the ROS produced by the porphyrin molecule under the condition of light stimulation destroys the interaction between the hydrogen bonds between the polypeptide chains, thus destroying the original self-assembly process and the light. The inhibition effect of porphyrin driven molecules was sustained under no sustained light stimulation. (3) the effect of porphyrin molecules with mature amyloid peptide fiber was further degraded by light driven porphyrin molecules to drive porphyrin molecules to degrade mature fibers.

【學(xué)位授予單位】：江蘇大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R587.1

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