Lead Optimization of MTL1-44 for Antibacterial Efficacy Against Staphylococcus aureus

Abstract

Antimicrobial-resistant strains of bacterial pathogens like Staphylococcus aureus are becoming more prominent each year, highlighting the need for alternative antibacterial agents. Peptoids, peptide mimics with side chains on the amide nitrogen (N-substituted oligoglycines), are one class of compounds with growing interest due to improved stability and bioavailability compared to that of peptides. MTL1-44, a peptoid discovered in the Bicker Lab, has shown promising levels of antibacterial activity against S. aureus while retaining low cytotoxicity. The focus of this study is on performing lead optimization of MTL1-44 via structural modi􀏐ications to improve its antibacterial ef􀏐icacy. Utilizing solid-phase synthesis, a sarcosine scan was done to better understand the structure-activity relationship (SAR) within the peptoid. Antibacterial activity will be evaluated through minimum inhibitory concentration (MIC) testing.