As a important part of the innate immune system of all organisms, antimicrobial peptides (AMPs), also called peptide antibiotics when nontoxic for humans, are considered as possible solution for fighting bacteria resistant to standard antibiotics. Crucial characteristic of potential lead compound for therapeutic applications is high selectivity, parameterized as the ratio of the haemolytic activity defined as the HC50 against erythrocytes and minimal inhibitory concentration (MIC) against the reference bacterium Escherichia coli. The “Designer” algorithm proposed adepantins (ADPs) - highly selective, alpha-helical, glycine and lysine rich peptides less than 50% homologous to any known AMP. ADPs were tested in their monomeric, dimeric and fluorescently labelled form. Tested against different bacteria strains they showed high selectivity for Gram-negative bacteria (MIC = 0.5 - 4 µM), especially E. coli. When tested on membrane permeabilization, different membrane models were used and ADPs showed rapid permeabilization of both membranes of E. coli. These tests provided insight in their mode of action. All monomeric ADPs have exceptionally low haemolytic activity, while dimers expressed certain toxicity against host cells. ADPs are proven to bind efficiently to the cell surface of the host cells without subsequent membrane damage. Gathered results confirmed that ADPs are indeed highly selective, novel, artificial AMPs.

Fizika,Kemija,Biologija

Ovaj doktorat je dobijen na doktorskom studiju biofizike Sveučilišta u Splitu, Prirodoslovno- matematički fakultet u Splitu, uz ko-mentorstvo prof. A. Tossija sa Sveučilišta u Trstu. Dobiveni akademski naziv i stupanj: doktorica prirodnih znanosti iz polja kemije.