基于POSS单层纳米结构的药物蛋白分离纯化研究

批准号:
22004100
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
张越
依托单位:
学科分类:
分离与分析
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
张越
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中文摘要
药物蛋白的有效分离纯化是研究其结构功能和开展临床应用的重要前提。鉴于此,本项目以Fc融合药物蛋白为模型,拟基于功能性笼状聚倍半硅氧烷(POSS)单层纳米结构,发展高品质的药物蛋白分离富集新方法。利用POSS的纳米尺寸、结构刚性和供/受体作用,实现其在氧化石墨烯表面的单层自组装,获得POSS单层纳米结构,抑制石墨烯基底对蛋白质的非特异性吸附,并提高后续功能配体和目标蛋白的负载容量;以金属配合物、聚-L-精氨酸与低聚物水凝胶为修饰配体,构建功能性POSS单层纳米结构文库,筛选出针对Fc结构域中不同作用位点的高性能吸附材料,并阐明其作用机制与分离特性;研究蛋白质在材料表面的吸附-洗脱行为,建立药物蛋白的选择性分离方法,实现复杂生物样品中Fc融合蛋白的高效、高选择性和高容量分离纯化。本项目将为特定药物蛋白的高精度、高准确性获取提供新策略,为药物蛋白质组学研究提供重要的理论和技术支撑。
英文摘要
The effective isolation of therapeutic proteins plays an essential role in studying their structural functions and clinical applications. In this project, new separation approaches with improved performances are developed on the basis of polyhedral oligomeric silsesquioxane (POSS)-based functional monolayer nanostructures to achieve the above aims, where Fc-fusion proteins are selected as model therapeutic proteins. By taking advantage of the nano-scale size, rigid structure and donor/acceptor effect of POSS, its monolayer self-assembly on the surface of graphene oxide is performed to fabricate the POSS-based monolayer nanostructures, which exhibit great resistance against non-specific adsorption of proteins, and facilitate the loading of functional ligands and target protein species. Metal complex, poly-L-arginine and oligomer hydrogel serve as affinity ligands to establish the POSS-based functional monolayer nanostructure libraries, by which the most suitable adsorbing materials for diverse interaction sites on the Fc region are screened. The quartz crystal microbalance technology is combined with molecular docking simulation to elucidate the selective binding mechanisms and separation characteristics. The protein adsorption and desorption behavior by these materials are studied, moreover, several approaches are developed and employed for highly efficient and selective separation of Fc-fusion proteins with superior capacity from complex biological samples. These works will provide novel strategies for the acquisition of specific therapeutic proteins with high accuracy and precision, as well as significant theoretical and technical supports for pharmacoproteomics research.
期刊论文列表
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专利列表
DOI:10.1016/j.seppur.2022.122152
发表时间:2022-09
期刊:Separation and Purification Technology
影响因子:8.6
作者:Kaiqiang Xie;Shaojie Wang;Mao-Sen Yuan;Hong Zhang;Hongxia Deng;Yue Zhang;Jinyi Wang;Yuting Zhuang
通讯作者:Kaiqiang Xie;Shaojie Wang;Mao-Sen Yuan;Hong Zhang;Hongxia Deng;Yue Zhang;Jinyi Wang;Yuting Zhuang
DOI:10.1016/j.foodchem.2021.131465
发表时间:2021
期刊:Food Chemistry
影响因子:8.8
作者:Yu-Ting Zhuang;Liuyimai Ma;Hao Huang;Lu Han;Li Wang;Yue Zhang
通讯作者:Yue Zhang
DOI:10.1016/j.coco.2021.100702
发表时间:2021-06
期刊:Composites Communications
影响因子:8
作者:Yue Zhang;Yuting Zhuang;R. Yin;Lu-lu Han;Yu-Lin Shen;Zhen Zhang;Kaiqiang Xie;Jianwei Zhang;Mao-Sen Yuan;Jinyi Wang
通讯作者:Yue Zhang;Yuting Zhuang;R. Yin;Lu-lu Han;Yu-Lin Shen;Zhen Zhang;Kaiqiang Xie;Jianwei Zhang;Mao-Sen Yuan;Jinyi Wang
DOI:10.1016/j.cej.2022.138989
发表时间:2022-09
期刊:Chemical Engineering Journal
影响因子:15.1
作者:J. Su;Mao-Sen Yuan;Lu-lu Han;Hongxia Deng;Jiahao Chang;Yuting Zhuang;Jinyi Wang;Yue Zhang
通讯作者:J. Su;Mao-Sen Yuan;Lu-lu Han;Hongxia Deng;Jiahao Chang;Yuting Zhuang;Jinyi Wang;Yue Zhang
国内基金
海外基金
