Abstract
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.