Design and characterization of novel hybrid peptides from LFB15(W4,10), HP(2-20), and cecropin A based on structure parameters by computer-aided method
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The increasing problem of antibiotic resistance among pathogenic bacteria requires development of new antimicrobial agents. The pivotal assets of the antimicrobial peptide include potential for rapid bactericidal activity and low propensity for resistance. The four new antimicrobial hybrid peptides were designed based on peptides LFB15(W4,10), HP(2-20), and cecropin A according to the structure–activity relationship of the amphipathic and cationic antimicrobial peptides. Their structural parameters were accessed by bioinformatics tools, and then two hybrids with the most potential candidates were synthesized. The hybrid peptide LH28 caused an increase in antibiotic activity (MIC50 = 1.56–3.13 μM) against given bacterial strains and did not cause obvious hemolysis of rabbit erythrocytes at concentration of 3.13 μM with effective antimicrobial activity. The results demonstrate that evaluating the structural parameters could be useful for designing novel antimicrobial peptides.
KeywordsAntimicrobial peptides Design Structure parameters Computer-aided method
This study is supported by National Natural Science Foundation of China (No. 30771574; No. 30810303084), Beijing Natural Science Foundation (No. 415062031), and Chinese 863 Program (No. 2004AA246040).
- Lee DG, Kim HN, Park Y, Kim HK, Choi BH, Choi CH, Hahm KS (2002) Design of novel analogue peptides with potent antibiotic activity based on the antimicrobial peptide, HP (2-20), derived from N-terminus of Helicobacter pylori ribosomal protein L1. Biochim Biophys Acta 1598:185–194CrossRefGoogle Scholar
- Rodríguez-Hernández MJ, Saugar J, Docobo-Pérez F, de la Torre BG, Pachón-Ibáñez ME, García-Curiel A, Fernández-Cuenca F, Andreu D, Rivas L, Pachón J (2006) Studies on the antimicrobial activity of cecropin A-melittin hybrid peptides in colistin-resistant clinical isolates of Acinetobacter baumannii. J Antimicrob Chemother 58:95–100CrossRefGoogle Scholar
- Saugar JM, Rodríguez-Hernández MJ, de la Torre BG, Pachón-Ibañez ME, Fernández-Reyes M, Andreu D, Pachón J, Rivas L (2006) Activity of cecropin A-melittin hybrid peptides against colistin-resistant clinical strains of Acinetobacter baumannii: molecular basis for the differential mechanisms of action. Antimicrob Agents Chemother 50:1251–1256CrossRefGoogle Scholar
- Tossi A, Sandri L, Giangaspero A (2002) New consensus hydrophobicity scale extended to non-proteinogenic amino acids. In: Benedetti E, Pedone C (eds) Peptides 2002: Proceedings of the twenty-seventh European peptide symposium. Edizioni Ziino, Napoli, pp 416–417Google Scholar
- Wang YZ, Wang ZQ, Xu ZR (2004) Comparison of antimicrobial activity in vitro of antimicrobial peptides and antibiotics against gram-positive and gram-negative bacteria. Chin J Vet Sci 24:270–273Google Scholar