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Updated: May 4, 2026

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
Dimeric unnatural polyproline-rich peptides with enhanced antibacterial activity
Victor Hernandez-Gordillo1, Iris Geisler1, Jean Chmielewski1
1Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47901, USA.
Abstract:
We report a dimerization strategy to enhance the antibacterial potency of an otherwise weak cationic amphiphilic polyproline helical (CAPH) peptide. Overall, the dimeric CAPHs were more active against Escherichia coli and Staphylococcus aureus than the monomeric counterpart, reaching up to a 60-fold increase in potency. At their minimum inhibitory concentration (MIC), the dimeric peptides demonstrated no hemolytic activity or bacterial membrane disruption as monitored by β-galactosidase release in E. coli. At higher concentrations the dimeric agents were found to induce β-galactosidase release, but maintained negligible hemolytic activity, pointing to a potential shift in the mechanism of action at higher concentrations. Thus, discontinuous dimerization of an unnatural proline-rich peptide was a successful strategy to create potent de novo antibacterial peptides without membrane lysis.
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