Peptoids are peptidomimetic polymers that are resistant to proteolysis and less prone to immune responses; thus, they can provide a practical alternative to peptides. Among the various therapeutic applications that have been explored, cationic amphipathic peptoids have demonstrated broad-spectrum antibacterial activity, including activity towards drug-resistant bacterial strains. While their potency and activity spectrum can be manipulated by sequence variations, bacterial selectivity and systemic toxicity need to be improved for further clinical development. To this aim, we incorporated various hydrophobic or cationic residues to improve the selectivity of the previously developed antibacterial peptoid 1. The analogs with hydrophobic residues demonstrated non-specific cytotoxicity, while those with an additional cationic residue showed improved selectivity and comparable antibacterial activity. Specifically, compared to 1, peptoid 7 showed much lower hemolysis and cytotoxicity, while maintaining the antibacterial activity. Therefore, we believe that peptoid 7 has the potential to serve as a promising alternative to current antimicrobial therapies.

拟肽是拟肽聚合物，对蛋白水解有抵抗力，不易产生免疫反应。因此，它们可以提供肽的实用替代品。在已探索的各种治疗应用中，阳离子两亲拟肽已证明具有广谱抗菌活性，包括对耐药细菌菌株的活性。尽管它们的效能和活性谱可以通过序列变化来控制，但细菌的选择性和全身毒性仍需改善，以进行进一步的临床开发。为此，我们引入了各种疏水或阳离子残基，以改善先前开发的抗菌肽1的选择性。。具有疏水残基的类似物表现出非特异性的细胞毒性，而具有额外阳离子残基的类似物表现出更高的选择性和相当的抗菌活性。具体而言，与1相比，类肽7表现出低得多的溶血和细胞毒性，同时保持了抗菌活性。因此，我们认为类肽7 有潜力成为当前抗菌疗法的有希望的替代品。