基于功能基元组合策略的双重靶向性抗菌高分子的设计与构建

功能高分子的研究的核心问题实际上是功能基元与序构的问题，高分子链上的重复单元和它们的排布方式直接决定了其功能与性质。目前，抗菌高分子作为一种新的对抗耐药性的方案得到了广泛的关注，这类化合物一般由正电荷与疏水链功能基元组成，该组合可通过物理方式破坏细菌细胞膜从而达到无视抗药性的杀菌效果。然而，抗菌高分子存在有细胞毒性和血清稳定性上的短板，对抗菌高分子进行结构多样化和活性筛选优化的效率也很低，这些都很大程度上限制了其发展与应用。因此，本项目力图采取“由下至上”的策略，通过对抗菌高分子的功能基元和序构进行新的设计来引入额外的抗菌机理，同时通过组合化学方法实现功能基元的组合与高分子的高通量合成，从而借由双重机理的协同作用和规模化筛选来进一步提高抗菌高分子的性能，为解决细菌抗药性问题提供新的潜在解决方案。

The key of research in functional macromolecules is about elementary functionality units, their sequence and composition. The repeating units and their sequence on a polymer chain directly determine the macromolecule's property and function. Currently, antimicrobial polymer as a new solution for antibiotic resistance has received widespread attention. This type of materials generally has cationic charges and hydrophobic moieties as elementary functionality units, the combination of which disrupts bacterial cell membrane and kills the bacteria in a resistance-irrelevant way. However, most antimicrobial polymers suffer from their eukaryotic cytotoxicity and low serum stability, and it is difficult to prepare antimicrobial polymers of diverse structures in a efficient way, which makes screening and optimization costly and time consuming. To remove these barricades that limit such polymers' development and application, this proposal aims to take a bottom-up approach in the design of polymer's elementary functionality units and their sequence, thus introducing additional antimicrobial mechanisms. Meanwhile, combinatorial chemistry approach may be utilized to combine these elementary functionality units, form antimicrobial polymers in a high-throughput way. Thus, synergistic effect from dual antimicrobial mechanisms and high-throughput screening may work together to further enhance the performance of antimicrobial polymers, revealing a new possible solution for antibiotic resistance.