engleski

Peptide antibiotics: do they have a future or not?

Running out of time to find efficient antimicrobial agents for treatment of bacterial infections and out of species richly endowed with host defense peptides (as potential new generation antibiotics) is common threat to civilization gains. When our own body produces a spectrum of antimicrobial peptides (AMPs) capable of fending off microbial pathogens in cooperation with immune cells, why we still cannot walk into any pharmacy and buy peptide antibiotics also capable of discharging bacteria by creating transient pores in their cytoplasmic membrane (1)? We shall focus on AMPs toxicity and inadequate therapeutic index as main obstacles for their commercial applications. Several in-silico methods will be offered for finding new AMPs in endangered species and for designing their analogues with excellent activity and very high selectivity tested in vitro (2-7). 1. H.V. Westerhoff, D. Juretic, R.W. Hendler, M. Zasloff, “Magainins and the distruption of membrane-linked free-energy transduction”, Proc. Natl. Acad. Sci. USA 86, 6597-6601 (1989). 2. 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). 3. D Juretić, D Vukičević, D Petrov, M Novković, V Bojović, B Lučić, N Ilić, A Tossi: “Knowledge-based computational methods for identifying or designing novel, non-homologous antimicrobial peptides”, Eur. Biophys. J. 40, 371-385 (2011). 4. 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). 5. M Novković, J Simunić, V Bojović, A Tossi, D Juretić: “DADP: the Database of Anuran Defense Peptides”, Bioinformatics 28, 1406-1407 (2012). 6. N Ilić, M Novković, F Guida, D Xhindoli, M Benincasa, A Tossi, D Juretić : “Selective antimicrobial activity and mode of action of adepantins, glycine-rich peptide antibiotics based on anuran antimicrobial peptide sequences”, Biochim. Biophys. Acta (in press 2012). 7. N Kamech, D Vukičević, A Ladram, C Piesse, J Vasseur, V Bojović, D Juretić: “Improving the therapeutic potential of natural peptide antibiotics”, J. Chem. Inf. Model. 3341-3351 (2012).

peptide antibiotics; in-silico search; selectivity

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