侧链功能化多肽的分子设计、制备与性能研究

发布时间：2018-01-03 13:24

本文关键词：侧链功能化多肽的分子设计、制备与性能研究　出处：《华南理工大学》2016年硕士论文　论文类型：学位论文

【摘要】：合成多肽和天然多肽一样具有α-螺旋和β-折叠等二级结构,拥有诸多特殊的性质,包括可生物降解、良好的生物相容性、低毒、独特的结构和功能以及自组装能力等。作为天然多肽和蛋白质的类似物,它常被用来模拟蛋白质的结构和性能,实现多样的功能化。制备合成多肽的方法是α-氨基酸-N-羧基环内酸酐(NCAs)开环聚合法(ROP),然而由这种方法制备的多肽是均聚多肽,氨基酸序列单一、多肽链长度具有分散性、而且通常无生物活性,因此其物理化学性能单一,不能够有效地模拟天然多肽或蛋白质的结构与功能。为此,应用适当的化学改性技术增加多肽化学结构的复杂性,使之更好地模拟天然多肽和蛋白质的物理、化学和生物性质,甚至可以赋予其新的功能性(例如温敏性、光敏性、pH响应性等),极大地推动了生物医用材料的发展,是目前针对合成多肽研究的焦点。本文正是基于开环聚合法合成多肽,再结合点击化学修饰法对多肽侧链进行改性,制备具有温敏性的功能化多肽。进而深入地探讨多肽的二级结构、LCST行为和自组装行为与多肽结构的关系,旨在为开发新型多肽类生物医用材料奠定理论基础。主要内容如下:(1)设计多种含炔基、烯基的NCAs单体,合成一系列具有不同聚合度和侧链长度的可点击的均聚多肽或多肽基嵌段共聚物。通过开环聚合法实现了低聚合度多肽的可控聚合。(2)利用“巯-烯”和“巯-炔”点击在多肽侧链上接枝乙二醇类功能性分子,并对接枝后的侧链氧化改性,引入砜结构。结果表明,点击反应可以高效地实现侧链接枝,接枝率高达100%;用乙酸-双氧水体系可成功对侧链氧化改性。(3)利用傅里叶变换红外光谱(FTIR)和圆二色光谱(CD)对多肽的二级结构进行表征。结果表明,多肽的二级结构受聚合度、侧链长度、单个侧链上接枝的功能性分子个数、温度和侧链氧化等多个因素的影响。(4)利用紫外吸收光谱(UV-Vis)探讨多肽的LCST行为,并探讨聚合度、侧链氧化对温敏性的影响。结果表明,侧链乙二醇化后,部分均聚多肽具有明显的温敏性,其LCST行为具有可逆性和持久性,侧链砜结构的引入使其温敏性消失。值得注意的是侧链乙二醇化的低聚合度聚(烯己基-L-谷氨酸酯)(PHLG-S-3PEG)在侧链氧化后具有明显的温敏性。聚合度影响多肽的LCST行为,聚合度低的均聚多肽具有较高的LCST。(5)利用动态光散射法(DLS)探讨不同温度下多肽基嵌段共聚物在水溶液中的自组装行为。结果表明,侧链乙二醇化的聚(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)在侧链氧化后水溶性显著提高,其自组装行为受温度的影响。
[Abstract]:Like natural peptides, synthetic peptides have the secondary structures of 伪 -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 伪 -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.
【学位授予单位】：华南理工大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O631.3;O629.72

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