抗酶解功能型仿生多肽自组装软物质纳米材料

Peptides, as a unique platform for building-up novel biofunctional materials, have attracted great attention and made rapid progress over the last 10 years due to many primitive advantages,such as mild synthesis condition, easy functionalization, low cost and fast preparation, biocompatibility and bioactivity. Furthermore, through molecular self-assemblies, peptides can also give rise to a range of well-defined nanostructures from nanotubes, nanofibers, nanoparticles and nanotapes to nanorods. These advantages have ensured the promise of these molecules as excellent candidate for different biomedical applications, such as biosensors, drug deliveries and bioelectronics and tissue engineering. However, the inherent susceptibility towards enzymatic hydrolysis and short lifetime of peptidic molecules in vivo reduce their efficiency and limit their scope of applications when long-term bioavailability is required. Although active efforts have focused on designing and synthesizing non-peptidic molecules from a large pool of unnatural amino acids to achieve prolonged or controlled stability and bioavailability of those molecules, it remains a challenge to depend on peptidic analogues entirely made of D-amino acids or β-amino acids to achieve the functions of native peptides because the changes of the stereochemistry of the peptide motif, unavoidably, lead to the loss of their functions. Inspired by nature in which biological systems selectively incorporate glycoside to L-peptides to enhance their biostabilities, we propose to prepare a series of novel peptide derivatives through systematic modifications of L-peptide side chain with a variety of glycoamino acid entities, respectively. From this proposed study, we expect to evaluate the effects of skeletal modification on their biostability and the self-assembling behaviors of the corresponding glycopeptide. The systemic modification of peptidic molecules can not only improve their biostabilities, but also play a good role in the regulation of the secondary structures of the natural peptides together with their self-assembly capabilities to generate diverse molecular self-assembly aggregates and functional entities.

多肽作为仿生生物分子材料的构筑基元，由于其良好的生物相容性、生物活性和自组装方面的优点，一直是备受关注的研究材料。但是该分子在生物体内生物半衰期短、生物稳定性差的缺点严重限制其在生物医药领域的应用。从自然界蛋白质物质抵抗蛋白酶降解的方法受到启发,申请人利用单糖分子对多肽分子侧链实行选择性的修饰，进而实现多肽分子的局部构象的调整达到抵制蛋白酶对其分子的识别和降解的效果。同时多肽分子骨架结构的系统性改造不仅可以提高多肽分子生物稳定性，也会对丰富天然多肽分子的二级结构和自组装能力起到良好的调节作用，生成多样化的分子自组装聚集体和功能体，并为制备新型的仿生多肽小分子自组装水凝胶提供一个新的构筑基元。

本项目通过整合具有自组装特性的多肽分子和单糖分子，构建了一系列具有糖化修饰程度和位点不同的糖肽分子，并系统研究了多肽糖化修饰对调节多肽分子的自组装特性、纳米形貌、力学性能、热力学和生物稳定性，以及潜在的生物应用潜力，做了详细而深入的研究和探索，并得到了结论性的数据。首先，基于多肽固相合成以及液相有机合成方法制备了一系列具有单糖定点修饰的糖肽分子，并证明了该合成方法和制备路线的可行性；其次，系统研究糖化修饰对多肽分子自组装能力和微观纳米结构、力学性能、热力学和生物稳定性的影响规律；最后，探索该系列糖肽自组装体在制备具有良好抑制细菌存活，同时又能促进细胞生长的培养基体上的应用潜力。该项研究课题的开展不仅可以丰富目前具有自组装特性的多肽的多样性，完善其自组装能力和特性，并为制备新型的仿生多肽系列自组装水凝胶提供了一种新的构筑基元。