Design of sugar amino acid containing selective antimicrobial peptides: synthesis with flow peptide synthesis and in vitro evaluation

During our work we synthetize and in vitro characterize antimicrobial peptide derivatives. Their therapeutic application can be greatly hampered by their high hemolytic effect, toxicity and aggregation tendency. Based on the literature, the alteration of their sequences with proteogenic and non-natural amino acids may favorably affect the selectivity and antimicrobial activity of these peptides. In this study, we plan to modify the original sequences with hydrophilic / hydrophobic sugar amino acids to increase the solubility and selectivity of the new analogs. Continuous flow peptide synthesizer is one of the best alternative methods to incorporate expensive or/and non-natural amino acids into sequences. Peptides, foldamers and chimera peptides can be synthetized with this cost-effective method. In our cooperation, we plan to produce sugar amino acid modified peptide analogs with the continuous flow peptide synthesizer located at the Laboratory of Structural Chemistry and Biology of ELTE.

In vitro studied are planned to define the structure – activity relationship of the prepared peptide derivatives. We investigate the antibacterial effect and the selectivity of the peptides. Then, determine the new analogs’ cytotoxic, hemolytic and cytostatic effects on cell cultures modeling potential host cells.

Viktória Goldschmidt Gőz, Lilla Horváth