基于活性/可控自由基聚合技术的蛋白质抗原决定基印迹新方法研究

Proteins play a crucial role in the area of biomolecular recognition. The highly selective recognition and screening of target proteins is an important prerequisite for the research of proteins. In recent years, selective recognition of proteins was achieved throughout the molecularly imprinted technology. However, the barely satisfactory stabilization of protein template and unmanageable morphology of the imprinted shell are still the short slabs for specific recognition of the aim protein. To improve the efficiency and selectivity for the protein recognition further, this project intends to select epitope with well physics and chemical stabilization and simple structure to take place to the whole protein molecule as the imprinted template. Additionally, by the method of controlled living radical polymerization, the morphology and thickness of surface imprinted shell could be under control. With the combination of the epitope imprinted strategy and controlled living radical polymerization mentioned above, new methods for the preparation of imprinted materials with high recognized ability and selectivity are developed to provide important technical support for aim protein recognition and screening in the complex sample with high selectivity.

蛋白质在生物分子识别方面起到至关重要的作用。目标蛋白的高选择性识别与筛选是人类对蛋白质研究的重要前提。近年来通过分子印迹技术实现了蛋白质的选择性识别，然而蛋白模板稳定性不佳和形成表面印迹识别层的可控性这两方面因素仍然是印迹材料对目标蛋白特异性识别能力提升的重要制约因素。为进一步提高对目标蛋白的识别效率和识别选择性，本项目拟选择物理化学性质相对稳定、结构简单的抗原决定基小分子取代整个蛋白作为印迹模板，并通过活性/可控聚合反应实现表面印迹层的形貌与厚度可控。结合以上两个主要策略，建立制备更高识别能力和识别选择性印迹材料的新方法，并为复杂样品当中目标蛋白的高选择性识别与筛选提供重要的技术支撑。

目标蛋白的高选择性识别与筛选是人类对蛋白质研究的重要前提。通过分子印迹技术可以实现蛋白质的选择性识别，然而蛋白模板稳定性不佳和形成表面印迹识别层的可控性这两方面因素仍然是印迹材料对目标蛋白特异性识别能力提升的重要制约因素。本项目选择物理化学性质相对稳定、结构简单的抗原决定基小分子取代整个蛋白作为印迹模板，并通过可逆加成-断裂链转移（RAFT）自由基聚合实现表面印迹层的形貌与厚度可控。结合以上策略，发展了一系列以目标蛋白N-末端或C-末端抗原决定基作为模板，通过固载模板或固载链转移试剂进行印迹材料制备的技术路线，得到具有较高识别能力、识别效率与识别选择性的新型分子印迹材料，实现蛋白混合物样品中目标蛋白的高选择性识别。通过固载链转移试剂进行印迹材料制备的技术路线具有较好的普适性，而通过固载模板进行印迹材料制备的技术路线能够实现较高的蛋白选择识别性能。以上结果为通过分子印迹策略对复杂生物样品当中目标蛋白的高选择性识别与筛选提供重要的支撑。