De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers
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Updated: Jun 24, 2026

Production and Testing of Antimicrobial Peptides and Their Mimics
Published on: April 10, 2026
Sungwook Choi1, Andre Isaacs, Dylan Clements
1Department of Biochemistry, University of Pennsylvania, 1009 Stellar Chance Laboratories, 36th and Hamilton Walk, Philadelphia, PA 19104, USA.
Abstract:
The emergence of drug-resistant bacteria has compromised the use of many conventional antibiotics, leading to heightened interest in a variety of antimicrobial peptides. Although these peptides have attractive potential as antibiotics, their size, stability, tissue distribution, and toxicity have hampered attempts to harness these capabilities. To address such issues, we have developed small (molecular mass <1,000 Da) arylamide foldamers that mimic antimicrobial peptides. Hydrogen-bonded restraints in the arylamide template rigidify the conformation via hydrogen bond formation and increase activity toward Staphylococcus aureus and Escherichia coli. The designed foldamers are highly active against S. aureus in an animal model. These results demonstrate the application of foldamer templates as therapeutics.
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