本文關鍵詞：側鏈功能化多肽的分子設計、制備與性能研究　出處：《華南理工大學》2016年碩士論文　論文類型：學位論文

  更多相關文章： 側鏈功能化多肽 α-氨基酸-N-羧基環(huán)內酸酐開環(huán)聚合法 點擊化學 二級結構 溫敏性 自組裝

【摘要】：合成多肽和天然多肽一樣具有α-螺旋和β-折疊等二級結構,擁有諸多特殊的性質,包括可生物降解、良好的生物相容性、低毒、獨特的結構和功能以及自組裝能力等。作為天然多肽和蛋白質的類似物,它常被用來模擬蛋白質的結構和性能,實現(xiàn)多樣的功能化。制備合成多肽的方法是α-氨基酸-N-羧基環(huán)內酸酐(NCAs)開環(huán)聚合法(ROP),然而由這種方法制備的多肽是均聚多肽,氨基酸序列單一、多肽鏈長度具有分散性、而且通常無生物活性,因此其物理化學性能單一,不能夠有效地模擬天然多肽或蛋白質的結構與功能。為此,應用適當?shù)幕瘜W改性技術增加多肽化學結構的復雜性,使之更好地模擬天然多肽和蛋白質的物理、化學和生物性質,甚至可以賦予其新的功能性(例如溫敏性、光敏性、pH響應性等),極大地推動了生物醫(yī)用材料的發(fā)展,是目前針對合成多肽研究的焦點。本文正是基于開環(huán)聚合法合成多肽,再結合點擊化學修飾法對多肽側鏈進行改性,制備具有溫敏性的功能化多肽。進而深入地探討多肽的二級結構、LCST行為和自組裝行為與多肽結構的關系,旨在為開發(fā)新型多肽類生物醫(yī)用材料奠定理論基礎。主要內容如下:(1)設計多種含炔基、烯基的NCAs單體,合成一系列具有不同聚合度和側鏈長度的可點擊的均聚多肽或多肽基嵌段共聚物。通過開環(huán)聚合法實現(xiàn)了低聚合度多肽的可控聚合。(2)利用“巰-烯”和“巰-炔”點擊在多肽側鏈上接枝乙二醇類功能性分子,并對接枝后的側鏈氧化改性,引入砜結構。結果表明,點擊反應可以高效地實現(xiàn)側鏈接枝,接枝率高達100%;用乙酸-雙氧水體系可成功對側鏈氧化改性。(3)利用傅里葉變換紅外光譜(FTIR)和圓二色光譜(CD)對多肽的二級結構進行表征。結果表明,多肽的二級結構受聚合度、側鏈長度、單個側鏈上接枝的功能性分子個數(shù)、溫度和側鏈氧化等多個因素的影響。(4)利用紫外吸收光譜(UV-Vis)探討多肽的LCST行為,并探討聚合度、側鏈氧化對溫敏性的影響。結果表明,側鏈乙二醇化后,部分均聚多肽具有明顯的溫敏性,其LCST行為具有可逆性和持久性,側鏈砜結構的引入使其溫敏性消失。值得注意的是側鏈乙二醇化的低聚合度聚(烯己基-L-谷氨酸酯)(PHLG-S-3PEG)在側鏈氧化后具有明顯的溫敏性。聚合度影響多肽的LCST行為,聚合度低的均聚多肽具有較高的LCST。(5)利用動態(tài)光散射法(DLS)探討不同溫度下多肽基嵌段共聚物在水溶液中的自組裝行為。結果表明,側鏈乙二醇化的聚(烯丙基-L-谷氨酸酯)-b-聚醚胺-b-聚(烯丙基-L-谷氨酸酯)(PALG-PPO-PEG)和聚(炔丙基-L-谷氨酸酯)-b-聚醚胺-b-聚(炔丙基-L-谷氨酸酯)(PPLG-PPO-PEG)在側鏈氧化后水溶性顯著提高,其自組裝行為受溫度的影響。
[Abstract]:Like natural peptides, synthetic peptides have the secondary structures of 偽 -helix and 尾 -folding, and have many special properties, including biodegradability, good biocompatibility and low toxicity. As a natural peptide and protein analogues, it is often used to simulate the structure and properties of proteins. The synthetic polypeptide was prepared by ring-opening polymerization of 偽 -amino acid -N-carboxylic anhydride NCAs. however, the polypeptide prepared by this method is homopolymer polypeptide. The amino acid sequence is single, the length of polypeptide chain is dispersive, and usually has no biological activity, so its physical and chemical properties are single, which can not effectively simulate the structure and function of natural peptides or proteins. The application of appropriate chemical modification techniques to increase the complexity of the chemical structure of peptides, make them better simulate the physical, chemical and biological properties of natural peptides and proteins, and even give them new functions (such as temperature sensitivity). The pH response of Guang Min has greatly promoted the development of biomedical materials and has been the focus of research on synthetic polypeptides. This paper is based on the ring-opening polymerization method to synthesize peptides. Then the polypeptide side chain was modified by click-chemical modification to prepare the thermo-sensitive functional polypeptide. Then the relationship between the secondary structure and the self-assembly behavior of the peptide and the structure of the polypeptide was discussed. The aim is to lay a theoretical foundation for the development of new polypeptide biomedical materials. The main contents are as follows: (1) designing a variety of NCAs monomers containing alkynyl and alkenyl groups. A series of clickable polypeptides or polypeptide block copolymers with different degree of polymerization and side chain length were synthesized. Using "mercaptopenes" and "mercaptoacetylene" to click on the polypeptide side chain grafted with ethylene glycol functional molecules. The side chain was oxidized and sulfone structure was introduced after grafting. The results showed that the click-through reaction could realize the side linked branch efficiently, and the grafting rate was up to 100%. The secondary structure of polypeptide was characterized by Fourier transform infrared spectroscopy (FTIR) and circular dichroism spectrum (CDCD). The secondary structure of polypeptide was determined by degree of polymerization, length of side chain and number of functional molecules grafted on a single side chain. Effects of temperature and side chain oxidation on LCST behavior and degree of polymerization of polypeptides were investigated by UV-Vis-UV absorption spectra. The effect of side chain oxidation on the temperature sensitivity. The results showed that the partial homopolymer polypeptides had obvious temperature sensitivity and the LCST behavior was reversible and persistent after side chain ethylene glycol. The temperature sensitivity of side chain sulfone disappeared due to the introduction of the structure of side chain sulfone. It is worth noting that the low degree of polymerization of side chain ethylene glycol (PHLG-S-3PEG). The degree of polymerization affects the LCST behavior of polypeptides. The polypeptide with low degree of polymerization has higher LCST. 5) the self-assembly behavior of polypeptide block copolymers in aqueous solution at different temperatures is studied by dynamic light scattering (DLSs). The results show that the self-assembly behavior of polypeptide block copolymers in aqueous solution is very high. Poly (allyl -L-glutamate) -b-polyether amine (allyl -L-glutamate) and poly (allyl -L-glutamate) and poly (propyl-L-glutamate) by side chain ethylene glycol. The water solubility of PPLG-PPO-PEG was significantly increased after the side chain oxidation of -b-polyether amine -b-poly (propargyl -L-glutamate). Its self-assembly behavior is affected by temperature.
【學位授予單位】：華南理工大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：O631.3;O629.72

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