序列可控人工核酸碱基高分子的离子效应研究

研究序列可控人工核酸碱基高分子的离子效应，对于阐明离子与核酸间的作用机理，实现遗传信息表达的调控和相关疾病的基因治疗，以及发展新型核酸材料具有重要意义。目前，由于缺乏结构明确的模型体系和精确表征链构象行为的方法，对核酸体系离子效应作用机制的理解仍有待提升。本项目中，拟利用合理设计、精准合成和精确测量相结合的方式，以明确化学组成和结构的人工核酸碱基高分子作为模型体系，开展其离子效应研究。具体而言，申请人拟高效制备具有核酸碱基种类、链长和序列结构等结构参数可控、且可变的模型核酸碱基高分子，研究溶液中和界面上离子种类与强度对核酸碱基高分子链构象行为的影响，从分子层次上明晰离子与核酸特定位点间的作用机理。在此基础上，进一步探索序列可控人工核酸碱基高分子在智能界面材料方面的应用。本项目的实施，将加深对核酸体系离子效应本质的认识，并为利用人工核酸碱基高分子构筑新型仿生材料提供研究思路。

Studying the ionic effects of synthetic sequence-controlled nucleobase-containing polymers is of great significance, which enables us to explain the interaction mechanism between ions and nucleic acids. Based on the ionic effects of nucleic acids, we can regulate the expression of genetic information, realize the genetic therapy of various diseases and develop new nucleic acid-based materials. Currently, an in-depth understanding of the ionic effects of nucleic acids is still not attained. This is mainly caused by the lack of a simple and efficient molecular model and the precise characterization of the chain conformational behavior. In the current project, we aim to combine rational design, precise synthesis, and accurate measurement to investigate the specific ion effect and the multivalent ion effect of synthetic nucleobase-containing polymers. The well-defined chemical constituents and simple structures of bio-inspired nucleobase-containing copolymers render them as a good molecular model system to investigate the ionic effects of nucleic acids. Specifically, a series of model nucleobase-containing copolymers with controlled and varied structural parameters (including nucleobase species, chain lengths and monomer sequences) will be prepared. The effect of distinct ions and their concentrations on the conformational behaviors of nucleobase-containing copolymers will be explored for polymer solutions and surface-attached polymer brushes, respectively. The interaction between ions and nucleic acids will be clearly understood at the molecular level. Further, we will exploit sequence-controlled nucleobase-containing copolymers to fabricate a smart responsive surface by using the interaction between ions and nucleobases. With the implementation of this project, it will not only deepen our understanding for the ionic effects of nucleic acids, but also provide a novel strategy for constructing bio-inspired materials from synthetic nucleobase-containing polymers.