基于酶-肽作用的可降解聚氨酯生物材料研究

In this work, we plan to introduce the protease sensitive active sites, like peptide bonds and pseudo peptide bonds into polyurethane to develop peptide mimetic biodegradable polyurethanes since the protease-peptide actions are effective and selective. The biologic studies have confirmed that one peptide bond may be effectively cleaved by corresponding protease, even the peptide or pseudo peptide existed in usual polymer chains. The protease-peptide actions can cause the degradation of polyurethane based on peptide bond cleaved by the action of protease. Firstly, some peptide and pseudo peptide including their derives will be designed and synthesized respectively, which are possible sensitive for our target proteases such as pepsin, trypsin and chymotrypsin existed in alimentary canal of human bodies. Then, these peptide and pseudo peptide are used as chain extenders to prepare series of biodegradable polyurethane, and acted as a cleavage sites by protease in polymer chains. However the synthesized biodegradable polyurethane will maintain the excellent mechanical properties and favorable biocompatibility of usual polyurethane because they have a microstructure of alternating soft and hard segments. We need to study the action mechanisms between protease and peptide or pseudo peptide, the effect of peptide and pseudo peptide structure on the cleavage efficiency, the properties of polyurethane etc. As a result, the biodegradation of polyurethane could be precisely controlled by adjusting the sorts and numbers of peptide bonds, the molecular structures and the protease concentration etc. We hope to find a novel method to prepare the biodegradable polymer with controllable degradation, and with desirable elasticity and attractive biodegradability of high selectivity and efficiency. The biodegradable polyurethane may mimetic the biological membranes, show fine qualities of biocompatibility and hemocompatibility, and can be used as scaffold materials in alimentary canal of human bodies.

基于蛋白酶与多肽的分子识别功能，即特定的蛋白酶通常只能与肽链中特定氨基酸形成的肽键(功能位点)作用，并非常高效、专一的将其打开为基础，设计并合成系列不同结构、长度的寡肽/伪寡肽，并通过化学反应将其引入聚氨酯中；结合聚氨酯良好的生物相容性和血液相容性，合成一系列含能被特定蛋白酶识别的功能位点的生物降解聚氨酯，探索建立一种基于蛋白酶分子识别功能的高效、可控的生物可降解聚氨酯材料的合成思路。主要对人体消化道中存在的蛋白酶敏感的寡肽/伪寡肽，被引入聚氨酯后其酶-肽作用的特异选择性及效率、作用机理、聚氨酯结构与降解特性的相互关系等，发现有效的聚氨酯生物医用材料中的蛋白酶-肽分子识别配对，为实现对其降解位点及过程的可控化、设计和开发可控降解消化道支架材料提供新的思路和支持。

基于蛋白酶与多肽的分子识别功能，即特定的蛋白酶通常只能与肽链中特定氨基酸形成的肽键(功能位点)作用，并非常高效、专一的将其打开为基础，主要对人体消化道中存在的蛋白酶敏感的寡肽/伪寡肽，设计并合成了苯丙氨酸-赖氨酸乙酯-苯丙氨酸（PLP）三肽、酪氨酸-富马酸-酪氨酸伪三肽(TFT)、寡聚赖氨酸（OPL）、赖氨酸-多巴胺（LDA）二肽等功能化合物，并作为扩链剂制备一系列能被特定蛋白酶识别的功能位点的生物降解聚氨酯，得到高效、可控的生物可降解聚氨酯材料。系统的研究了合成的聚氨酯的酶-肽作用的特异选择性及效率、作用机理、聚氨酯结构与降解特性的相互关系等，得到了有效的聚氨酯生物医用材料中的蛋白酶-肽分子识别对，为实现对其降解位点及过程的可控化、设计和开发可控降解消化道支架材料提供新的思路和支持。在此基础上，将氨基酸/肽键作为刺激响应功能单元引入药物控释系统和水凝胶中，制备新型的药物控释系统以及智能水凝胶。