基于荷电/糖基协同效应识别LDL的聚合物膜表面构建及其性能研究

项目名称： 基于荷电/糖基协同效应识别LDL的聚合物膜表面构建及其性能研究

项目编号： No.51473143

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 一般工业技术

项目作者： 黄小军

作者单位： 浙江大学

项目金额： 78万元

中文摘要： 人体血液中低密度脂蛋白(LDL)水平过高会引发一系列心脑血管疾病，严重威胁人类健康。如何进一步师法天然细胞膜表面LDL受体的结构和功能，研制出简单易得、高选择性识别LDL的吸附分离材料是一项材料科学与生物医学、高分子化学等交叉渗透的前沿而富有挑战的课题。本课题以天然LDL吸附材料和细胞膜表面LDL受体所具有的负电与糖单元共性结构为启发，以其独特的LDL高效识别功能特性为依据，创新性地提出基于荷电/糖基多重协同作用增强识别LDL的新构思，通过组合点击化学和主客体相互作用等方法制备出高选择性识别LDL的聚合物分离膜材料，阐明膜表面与蛋白质间相互作用机理，并揭示荷电种类、糖基结构(alpha-/beta-异构、差向异构、单糖/寡糖)、荷电/糖基密度及其分布等与荷电/糖基多重协同效应增强识别LDL蛋白质之间的内在关系；为新型LDL蛋白识别吸附分离材料的研制提供理论依据。

中文关键词： 聚合物分离膜；表面改性；低密度脂蛋白；协同相互作用；蛋白质识别

英文摘要： Abnormally high level of plasma low-density lipoprotein (LDL) in human plasma is a key pathogenic factor that contributes to atherosclerosis and finally leads to coronary artery diseases (CAD), which have been posing great threats to human health for years. Therefore, how to further develop the easily-prepared and highly-selective LDL adsorbents for separation processes, that bio-inspired from the structure and function of LDL receptors on plasmalemmas, has became a frontier, interdisciplinary and challenging research subject involving Material Science, Biomedical Engineering and Polymer Chemistry, etc. Herein, a new concept was accordingly innovated based on the 'Charge/Glycosyl' synergistic effect to improve the LDL recognition process, which was derived from the similar structures - the negatively charged ligands and the saccharide enriched domain in natural LDL adsorbents and plasmalemmal LDL receptors, for their extraordinary high effective recognitions to LDL. Polymer membranes with high affinity for LDL will be prepared via the 'Click' Chemistry and 'Host-guest' Interaction,and the mechanism of protein-membrane interaction will be elaborated in detail. Furthermore, intrinsic relationships between the key factors and the 'Charge/Glycosyl' synergistic effect will be demonstrated by designed experiments, including different charge types, saccharide structures (stereoisomerism, epimerism, repeating units), surface density and distribution, etc.to influence the LDL recognition process. Based on these research, we hope to offer a theoretical basis for the development of novel LDL adsorbents for protein recognition and separation.

英文关键词： Polymeric Membrane;Surface Modification;Low-density Lipo- protein;Synergistic Effect;Protein Recognition