Unexpected relationships between structure and function in α,β-peptides:: Antimicrobial foldamers with heterogeneous backbones

We describe our first effort to design antimicrobial α/β-peptides based upon their helical folding behavior. α/β-Peptide 3 (above), designed as a scrambled negative control, exhibited the most favorable activity profile, combining high antimicrobial activity with low hemolytic activity. This finding suggests that design principles focused primarily on structures that adopt globally amphiphilic structures may exclude productive possibilities from evaluation. Copyright © 2004 American Chemical Society.