多肽类靶向配体或分子探针的生物活性和稳定性可逆调控

项目名称： 多肽类靶向配体或分子探针的生物活性和稳定性可逆调控

项目编号： No.21305114

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 吴川六

作者单位： 厦门大学

项目金额： 25万元

中文摘要： 多肽作为靶向配体、分子探针和模型药物分子等在化学、生命分析、药学以及生物医学等领域都得到了非常广泛的应用。然而，多肽在生物体内极易被蛋白酶水解，这成为限制其进一步发展的主要障碍。因此，探索新的方法提高多肽在生物体内的稳定性，将具有重要意义。本项目拟探索将聚合物可控折叠概念应用于多肽分子生物性能的可逆调控，以克服多肽类靶向配体或分子探针在实际应用中易被蛋白酶水解的难题，从而提高其生物利用率。本项目将设计合成系列组成和结构不同的氧化还原响应型聚合物-多肽（cPMI）结合物。通过聚合物氧化折叠前后结构或位阻的不同，调控与之连接的多肽cPMI与周围环境分子间的接触或相互作用，从而对cPMI的稳定性和生物活性进行可逆调控。采用多种分析手段对合成的聚合物-cPMI结合物进行表征，并研究聚合物折叠前后cPMI的生物活性和抗酶水解性。此外，进一步研究多功能的聚合物-cPMI结合物在癌细胞内的生物效应。

中文关键词： 多肽；分子探针；聚合物；可控折叠；生物活性

英文摘要： Peptides that serve as targeting ligands, molecular probes and model drugs have been widely used in many areas such as chemistry, bioanalysis, pharmaceutics and biomedicine. However, peptides are prone to be rapidly degraded in biological systems, a limitation which significantly hampers their further development and application. It is thus very important and meaningful to develop novel strategies for improving the stability of peptides in biological milieu. In this project, we will develop an efficient and straightforward strategy to reversibly regulate the bioactivity and stability of peptide targeting ligands/molecular probes, which exploits the concept of controlled polymer folding, for the purpose of conquering the challenge of their propensity to be rapidly hydrolyzed in practical applications. We will design and synthesize a series of redox-responsive polymer-peptide (cPMI) conjugates with diverse compositions and structures. The stability and bioactivity of the conjugated cPMI can be reversibly tuned through controlling the change of the configuration or steric hindrance of peptide microenvironment before and after the redox-folding of the conjugates, a change which would strongly alter the propensity of interactions between cPMI and molecules in biological milieu. The synthesized polymer-cPMI conjugates

英文关键词： peptide；molecular probe；polymer；controlled folding；bioactivity