一种新型伤口愈合肽的设计及其在糖尿病足治疗中的应用研究

糖尿病足患者由于伤口愈合环节失控，加之细菌感染导致皮肤易损伤、难治疗以及易复发。糖尿病足发病机理复杂，导致相应的治疗药物研发相对困难。本项目通过模仿皮肤抗菌肽的多功能特性，基于前期的工作基础，利用多靶点药物设计策略，将RGD多肽分子与神经肽SP偶联合成一类新型的具有抗菌活性和伤口愈合活性的杂合肽。通过结构优化平衡这类杂合肽药物的抗菌活性、整合素受体激动活性和NK1受体激动活性，最终筛选出理想的多功能伤口愈合肽，用于皮肤溃疡并伴有感染的糖尿病足的治疗。通过本项目的研究，我们希望能够获得治疗糖尿病足的高效先导化合物，同时也为发展具有多靶点和多功能的新型伤口愈合肽药物进行探索。

The wound in diabetic foot patients is easy to occur, difficult to treat and easy to recur due to the bacterial infection and out of control of wound healing process. Because the pathogenesis of diabetic foot is multifaceted, the development of corresponding therapeutic drugs becomes relatively difficult. In this project, based on our previous studies, we designed a novel type of hybrid peptides with antimicrobial activity and wound healing activity by connecting the neuropeptide SP and RGD using the multi-target drug design strategy, which can mimic the antimicrobial peptides with multiple functions secreted from skin. The ideal wound healing peptides with multiple functions to treat the diabetic foot with ulcer and bacterial infection are obtained by balancing the antimicrobial activity, agonistic activity to integrin and NK1 receptor. In a short, we hope to obtain effective lead compounds to treat diabetic foot through this project, and simultaneously explore the development of novel wound healing peptides with multi-targets and multiple functions.