Naslov
Selective antimicrobial activity and mode of action of adepantins, glycine-rich peptide antibiotics based on anuran antimicrobial peptide sequences

Autori
Ilić, Nada ; Novković, Mario ; Guida, Filomena ; Xhindoli, Daniela ; Benincasa, Monica ; Tossi, Alesandro ; Juretić, Davor

Izvornik
Biochimica et biophysica acta. Biomembranes (0005-2736) 1828 (2013), 3; 1004-1012

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
antimicrobial peptide; helical peptide; membranolytic; selectivity index

Sažetak
A challenge when designing membrane-active peptide antibiotics with therapeutic potential is how to ensure a useful antibacterial activity whilst avoiding unacceptable cytotoxicity for host cells. Understanding their mode of interaction with membranes and the reasons underlying their ability to distinguish between bacterial and eukaryotic cytoplasmic cells is crucial for any rational attempt to improve this selectivity. We have approached this problem by analysing natural helical antimicrobial peptides of anuran origin, using a structure–activity database to determine an antimicrobial selectivity index (SI) relating theminimal inhibitory concentration against Escherichia coli to the haemolytic activity (SI=HC50/MIC). A parameter that correlated strongly with SI, derived from the lengthwise asymmetry of the peptides' hydrophobicity (sequencemoment), was then used in the “Designer” algorithm to propose novel, highly selective peptides. Amongst these are the ‘adepantins’, peptides rich in glycines and lysines that are highly selective for Gram- negative bacteria, have an exceptionally low haemolytic activity, and are less than 50% homologous to any other natural or synthetic antimicrobial peptide. In particular, they showed a very high SI for E. coli (up to 400) whilst maintaining an antimicrobial activity in the 0.5–4 μM range. Experiments with monomeric, dimeric and fluorescently labelled versions of the adepantins, using different bacterial strains, host cells and model membrane systems provided insight into their mechanism of action.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija, Biologija

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