Naslov
Adepantins, a new class of designed antimicrobial peptides

Autori
Novković, Mario

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, diplomski rad, diplomski

Fakultet
Prirodoslovno-matematički fakultet u Splitu

Mjesto
Split

Datum
07.10

Godina
2010

Stranica
99

Mentor
Juretić, Davor

Ključne riječi
Adepantins; antimicrobial peptides

Sažetak
The main driving force for this thesis were theoretical concepts of Prof. D. Juretić and good collaboration Prof. Juretić established with Tossi-Gennaro group at the University of Trieste. Early results coming from the interplay of theory and experimental verifications in the field of antimicrobial peptides are nicely described in the Prof. Juretić book Bioinformatika: rad membranskih proteina. Every computer model must have an experimental verification, either for confirmation of the accuracy of predictions or further improvement of the software based on experimental data. This is also the case with Adepantins. We have shown that for the given design parameters, three Adepantins from the series of seven do have high antimicrobial activity as indicated by low MIC and IC50 values, although only against Gram-negative bacteria as predicted. All Adepantins are α-helical peptides as indicated by their behavior in Isopropanol in SPB 10 mM and when in contact with prokaryotic PG/dPG liposomes. Furthermore, the peptides reach their near maximum value of α-helicity at 20% TFE in SPB 10 mM, which is also a favorable result. Since conformational transition does not occur when they are in contact with PC/SM/Ch liposomes, it is likely that their hemolytic activity against eukaryotic cells will be diminished, as indicated with ADP1 which has very low hemolytic activity (HC50 > 800) against human erythrocytes. Membrane permeabilization studies with PI and CENTA have indicated one of the possible reasons why dimerised peptides have higher antimicrobial activity (MIC = 0.5), by permeabilizing the outer and inner bacterial membranes at a much faster rate and higher degree than bodipylated and acetylated peptides. However, we still do not know the exact mechanism of action of our peptides, their intracellular targets or how exactly they permeabilize the membrane. Further experiments on Adepantins include additional bacterial kinetics studies performed on more sensitive strains of E. coli BW 2552 and E. coli waaP. Also HC50 values will be determined for our peptides, hemolytic concentration at which 50% of human red blood cells are lysed. With MIC and HC50 values, we will be able evaluate the therapeutic index (TI = HC50 / MIC) of our peptides as well.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija, Biologija

Napomena
Rad je napisan na engleskom jeziku, a ko-mentor je bio prof. dr. Alessandro Tossi sa Sveučiliša u Trstu, Italija

POVEZANOST RADA