National University of Singapore (NUS) pharmaceutical scientists have successfully applied all-hydrocarbon-stapling modification to improve the enzymatic stability of their previously reported β-hairpin antimicrobial peptides (AMPs) for combating multidrug-resistant bacteria.
There is growing attention on AMPs as an alternative source of antimicrobials to address antibiotic resistance among bacterial infections. Susceptibility to degradation by hydrolytic enzymes in the human body is a major barrier currently limiting their clinical potential. To improve the clinical profile of AMPs, researchers have explored different chemical modification strategies, such as all-hydrocarbon stapling. This strategy has shown promising results on α-helical AMPs, but is relatively underexplored among β-hairpin AMPs.
In their previous study, the research team led by Associate Professor Rachel Ee from the Department of Pharmacy, NUS designed a library of synthetic β-hairpin AMPs, from which a particular peptide, BTT3 was identified as a potent candidate.
In this work, now published in the Journal of Medicinal Chemistry, the scientists employed