Helicity Modulation Improves the Selectivity of Antimicrobial Peptoids

• DOI: 10.1021/acsinfecdis.0c00356
• Publication Date: 2020-08-31T16:47:51Z
• Authors: Ho Yeon Nam; Jieun Choi; S. Dinesh Kumar; Josefine Eilsø Ni...; Minkyu Kyeong; Sungrok Wang; Dahyun Kang; Yunjee Lee; Jiyoun Lee; Myung-Han Yoon; Sukwon Hong; Reidar Lund; Håvard Jenssen; Song Yub Shin; Jiwon Seo
• Keywords: Peptoid

The modulation of conformational flexibility in antimicrobial peptides (AMPs) has been investigated as a strategy to improve their efficacy against bacterial pathogens while reducing toxicity. Here, we synthesized library helicity-modulated peptoids by the position-specific incorporation helix-inducing monomers. displayed minimal variations hydrophobicity, which permitted specific assessment effect differences on activity and selectivity. Among moderately helical peptoids, most dramatic increase selectivity was observed peptoid 17, providing more than 20-fold compared fully 1. Peptoid 17 had potent broad-spectrum that included clinically isolated multi-drug-resistant pathogens. Compared pexiganan AMP, showed superior metabolic stability, could potentially reduce dosage needed, alleviating Dye-uptake assays high-resolution imaging revealed was, with many AMPs, mainly due membrane disruption. However, high reflected its unique characteristics, differential interactions between erythrocyte membranes. Our results suggest way distinguish different compositions solely helicity modulation, thereby improving toward cells maintenance activity.