Xie Jiayang, Hu Weilong, Feng Xi, Liu Zixin, Zhou Min, Liu Runhui
Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences Suzhou 215163 China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology Shanghai 200237 China
Chem Sci. 2025 Jul 4. doi: 10.1039/d5sc03968a.
The rapid evolution of drug-resistant pathogens and the lag in antibiotic development pose a severe threat to global public health. Host defense peptides (HDPs) have emerged as promising candidates due to their broad-spectrum antimicrobial activity and low resistance tendency. However, their practical application is hindered by poor proteolytic stability and high costs. Peptoids are ideal HDP mimics, as their characteristic side chain relocation from α-carbons to backbone nitrogen atoms confers superior proteolytic resistance. Nevertheless, their solid-phase synthesis remains inefficient and difficult to scale up. Recent advances in polymer chemistry enable the efficient synthesis of α-peptoid polymers, offering a promising platform for antimicrobial materials development. This perspective summarizes the progress in α-peptoid polymers research, focusing on monomer synthesis, polymerization reaction, and antimicrobial applications. We discuss their potential in the antimicrobial field and propose perspectives on current challenges and future directions, aiming to inspire further advances in the development of α-peptoid polymer-based antimicrobials with clinical application potential.
耐药病原体的快速进化以及抗生素研发的滞后对全球公共卫生构成了严重威胁。宿主防御肽（HDPs）因其广谱抗菌活性和低耐药倾向而成为有前景的候选物。然而，其实际应用受到蛋白水解稳定性差和成本高的阻碍。类肽是理想的HDP模拟物，因为其特征性的侧链从α-碳原子重新定位到主链氮原子赋予了卓越的蛋白水解抗性。尽管如此，其固相合成仍然效率低下且难以扩大规模。聚合物化学的最新进展使得α-类肽聚合物能够高效合成，为抗菌材料的开发提供了一个有前景的平台。这篇综述总结了α-类肽聚合物研究的进展，重点关注单体合成、聚合反应和抗菌应用。我们讨论了它们在抗菌领域的潜力，并就当前的挑战和未来方向提出了观点，旨在激发具有临床应用潜力的基于α-类肽聚合物的抗菌剂开发取得进一步进展。
