Naslov
Adepantins, computationally designed, glycine-rich peptide antibiotics, with low toxicity and very high G- selectivity

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

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
New Antimicrobials Workshop in Trieste, 25-26.5.2012 / Tossi, Alessandro - Trst : Edizioni Università di Trieste, 2012, 37-38

ISBN
978-88-8303-379-7

Skup
New Antimicrobials Project 2-nd Workshop. New Compounds & New Strategies for Antimicrobials

Mjesto i datum
Trst, Italija, 25.05.2012. - 26.05.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
adepantins; peptide antibiotics; therapeutic index

Sažetak
Adepantins (ADPs) are glycine-rich antimicrobial peptides (AMPs), constructed using the “Designer” algorithm, which is based on known characteristics of anuran AMPs [1]. Parameters used to predict the primary structure of ADPs include various physicochemical properties, such as lengthwise asymmetry and predicted therapeutic index (TI). ADP1 was previously tested and has shown high antimicrobial activity (MIC) against E. coli (2-4 microM) and low cytotoxic activity (HC50) against human red blood cells (480 microM). To confirm the high selectivity of peptides from this group, additional tests were performed for monomeric, dimeric and fluorescently labelled versions of ADP2 and ADP3, using different bacterial strains, host cells and model membrane systems. They are selective for Gram-negative bacterial cells (MIC = 0.5 - 4 microM) both with respect to human erythrocytes (HC50 > 400 microM for monomers), as with ADP1, and with respect to Gram-positive bacteria (MIC > 128 microM). Dimers have high haemolicity and exceptional antimicrobial activity. All adepantins structure as alpha helices when in contact with PG/dPG liposomes, while maintaining a random coil structure in the presence of PC/SM/Ch membranes. At sub-toxic concentrations, dimers exhibit much higher permeabilization of both bacterial membranes in various E. coli strains than monomers. The “Designer” algorithm thus identified novel AMPs less than 50% homologous to any other natural or synthetic AMP, highly selective for Gram-negative bacteria and with a high TI (up to 400). [1] D. Juretić, D. Vukičević, N. Ilić, N. Antcheva, A. Tossi, Computational design of highly selective antimicrobial peptides, J Chem Inf Model. 49, 2873-2882 (2009)

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija, Biologija

POVEZANOST RADA