Recent progress in the structure-activity relationship of antibacterial peptoids

Antimicrobial peptides (AMPs) have garnered interest as a promising therapeutic option due to their high potency against multidrug-resistant bacterial strains, primarily attributed to their amphiphilic cationic properties, which enable them to directly interact with bacterial cells via the negatively charged cell membrane, ultimately leading to bacterial cell death. The clinical use of AMPs is limited by cytotoxicity arising from poor selectivity between microbial and host membranes. Their susceptibility to enzymatic degradation and high manufacturing costs further constrain their use. These drawbacks of AMPs created an urgent need to find an alternative class of antibacterial molecules with enhanced structural features known as peptidomimetics. Peptoids are a new class of peptidomimetics that mimic the structure of AMPs, overcoming several of these drawbacks through resistance to proteolysis and efficient, low-cost synthesis of short sequences. This review provides a comprehensive overview of recent progress in the structure activity relationship of antibacterial peptoids, and critically evaluates how structural features influence biological outcomes.