Adapting antibacterial display to identify serum active macrocyclic peptide antibiotics.
bioRxiv : the preprint server for biology(2023)
Abstract
Traditional methods of natural antibiotic discovery are low throughput and cannot keep pace with the development of antimicrobial resistance. Synthetic peptide display technologies offer a high-throughput means of screening drug candidates, but rarely consider functionality beyond simple target binding and do not consider retention of function . Here, we adapt a function-based, antibacterial display technology to screen a large library of peptide macrocycles directly for bacterial growth inhibition in human serum. This screen identifies an optimized non-toxic macrocyclic peptide antibiotic retaining function, suggesting this advancement could increase clinical antibiotic discovery efficiency.
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Key words
antibiotic discovery, macrocycle, bacterial display, antimicrobial peptide, serum
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