Naslov
Bioinformatics of Antimicrobial Peptides: From Collecting Data to Web Servers for Automatic Design of Peptide Antibiotics

Autori
Juretić, Davor

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

Izvornik
HRVATSKA AKADEMIJA ZNANOSTI I UMJETNOSTI: NOVA DOSTIGNUĆA HRVATSKIH ZNANSTVENIKA IZ BIOINFORMATIKE I BIOLOŠKE FIZIKE / Paar, Vladimir - , 2013

Skup
NOVA DOSTIGNUĆA HRVATSKIH ZNANSTVENIKA IZ BIOINFORMATIKE I BIOLOŠKE FIZIKE S NAGLASKOM NA GLAVNE TEME: GENOMIKA, PROTEOMIKA I STANIČNA DINAMIKA

Mjesto i datum
Zagreb, Hrvatska, 21.11.2012

Vrsta sudjelovanja
Plenarno

Vrsta recenzije
Nije recenziran

Ključne riječi
bioinformatics; antimicrobial peptides; antibiotics; Mutator; Designer; therapeutic index

Sažetak
Peptide antibiotics, either man-made or natural, are with us more than 20 years, but never delivered expectations of broad medical usage and of being replacement for ever less useful beta-lactam antibiotics against multiple resistant bacterial strains. Our research during past several years was directed toward finding new natural peptide antibiotics and toward design of analogues of antimicrobial peptides (AMPs) with significantly greater therapeutic index and decreased toxicity against human cells. The basic action needed to reach these goals consisted in collecting data about sequence, structure and biological activity of natural AMPs. Such data, originating from skins of frogs and toads, were collected from published papers and from Uniprot and sorted in the DADP database(1). It turned out that conserved signal peptides from AMP precursors can be used for an indirect search among all EST sequences, which was successful in finding novel classes of natural AMPs(2). We also designed novel AMP classes, containing peptides less than 50% identical to any known natural or man-made AMPs. The Designer algorithm performed automatic design of peptide antibiotics, named adepantins, predicted to have high therapeutic index (TI) and confirmed in experiments as having very high TI and specificity for slightly pathogenic E. coli strain(3-5). The Mutator algorithm had more modest goal to introduce just one or two amino acids as substitutions in parent AMPs, which Mutator predicted to have much higher TI after these substitutions. This was verified in experiments showing that Mutator’s suggested analogues with two substitutions have broad spectrum activity (against multiple resistant strains too) and very high TI(6). DADP, TI-predictor, and Mutator are available as easy to use on-line servers. 1) Mario Novković, Juraj Simunić, Viktor Bojović, Alessandro Tossi and Davor Juretić: "DADP: the Database of Anuran Defense Peptides" Bioinformatics J. 28, 1406-1407 (2012). 2) Valentina Tessera, Filomena Guida, Davor Juretić and Alessandro Tossi: "Identification of antimicrobial peptides from teleosts and anurans in expressed sequence tag databases using conserved signal sequences" FEBS Journal 279, 724–736 (2012). 3) Davor Juretić, Damir Vukičević, Nada Ilić, Nikolinka Antcheva and Alessandro Tossi: "Computational Design of Highly Selective Antimicrobial Peptides" J. Chem. Inf. Model. 49, 2873-2882 (2009). 4) Davor Juretić, Damir Vukičević, Dražen Petrov, Mario Novković, Viktor Bojović, Bono Lučić, Nada Ilić and Alessandro Tossi: “Knowledge-based computational methods for identifying or designing novel, non-homologous antimicrobial peptides“. Eur. Biophys. J. 40, 371-385 (2011). 5) Nada Ilić, Mario Novković, Filomena Guida, Daniela Xhindoli, Monica Benincasa, Alessandro Tossi, Davor Juretić: “Selective antimicrobial activity and mode of action of adepantins, glycine-rich peptide antibiotics based on anuran antimicrobial peptide sequences” BBA-Biomembranes (2012) Accepted. 6) Nédia Kamech, Damir Vukičević, Ali Ladram, Christophe Piesse, Julie Vasseur, Viktor Bojović, Juraj Simunić and Davor Juretić: “Improving the selectivity of antimicrobial peptides from anuran skin”. Journal of Chemical Information and Modeling (2012) In press: http://dx.doi.org/10.1021/ci300328y

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija, Biologija

POVEZANOST RADA