模拟宿主防御性蛋白的新型抗细菌氨基酸聚合物的设计、合成及功能研究

宿主防御性蛋白（HDP）具有广谱抗菌活性和不易产生抗药性的优点，为解决细菌抗药性的严峻挑战提供了可能。但是，HDP价格昂贵且易被蛋白酶水解，应用受到很大限制。本研究拟以α-和γ-氨基酸聚合物模拟HDP，克服HDP的上述缺点。通过抗细菌活性和其它生物活性测试、稳定性及生物可降解性能测试、以及细菌抗药性测试，对合成的氨基酸聚合物进行功能评价和逐步优化。预期获得易于制备、具有广谱高效抗细菌活性、高选择性、不易产生抗药性、结构稳定又可生物降解的更加优化的抗细菌聚合物。通过系统性的抗细菌氨基酸聚合物研究工作，加深对于HDP模拟物的基础理论研究和认识，并为最终获得具有自主知识产权的新型抗细菌药物打下基础。

Host defense peptides (HDP) have broad spectrum antimicrobial activity and low susceptibility to antimicrobial resistance, and are considered as promising antibacterial candidates to defeat the challenge of antimicrobial resistance in bacteria. However, the application of HDP is limited because HDP are very expensive and easily hydrolyzed by protease. In this study, α-and γ-amino acid polymers will be explored as mimics of HPD to overcome the shortcomings of HDP. These synthetic polymers will be evaluated and optimized through stepwise structural modification, based on antibacterial and other biological activity study, biodegradability analysis, and antimicrobial resistance study. We expect to obtain superior amino acid polymers that are easily prepared and have broad spectrum and potent antibacterial activity, high bacteria vs. mammalian cell selectivity, low susceptibility to antimicrobial resistance, good stability and reasonable biodegradability. The systematic study on antibacterial amino acid polymers will contribute to the fundamental understanding of HDP mimics and the obtaining of new antibacterial drugs with independent intellectual property rights in the future.