Development and characterization of novel antimicrobial compounds

New approaches of innovative alternative treatments against bacterial and viral infections are urgently needed in human medicine, and peptides represent a promising strategy. Peptides can be synthetic and consist of short amino acid sequences that can be chemically modified to more efficient forms and express bactericidal activity against a wide range of microbes.

The peptide optimization procedure includes generation of a peptide library, based on a known sequence, followed by initial predictions of their characteristics, including iso-electric point, net charge at pH 7, and percentage of hydrophobic, acidic, basic, and neutral residues. Furthermore, the structures, antimicrobial, and hemolytic activities of the peptides are predicted prior to synthesis and screening in biological systems. The activity spectrum of the lead compound can be further enhanced by additional modifications, including amidation, conjugation of a fatty acid chain, PEGylation, and amino acid substitution.

The main objective of this project is to design and carefully optimize and characterize novel peptidomimetic compounds derived from naturally occurring antimicrobial peptides, with the aim to identify novel antimicrobial compounds with low toxicity and improved antimicrobial activity towards a broader spectrum of bacterial species. The systematic design approach developed in our group allows for development of novel antimicrobial compounds, where several of the inherent limitations of antimicrobial peptides can be circumvented.

Articles
Wiman E, Elisa Z, Aili D, Bengtsson T, Selegård R, Khalaf H. (2023). Development of novel broad-spectrum antimicrobial lipopeptides derived from Plantaricin NC8 β. Sci. Rep. 13:4104.