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Applied Microbiology and Biotechnology

, Volume 82, Issue 6, pp 1097–1103 | Cite as

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

  • Zi-gang Tian
  • Tian-tang Dong
  • Da Teng
  • Ya-lin Yang
  • Jian-hua WangEmail author
Applied Genetics and Molecular Biotechnology

Abstract

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.

Keywords

Antimicrobial peptides Design Structure parameters Computer-aided method 

Notes

Acknowledgments

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).

References

  1. Arrighi RB, Nakamura C, Miyake J, Hurd H, Burgess JG (2002) Design and activity of antimicrobial peptides against sporogonic-stage parasites causing murine malarias. Antimicrob Agents Chemother 46:2104–2110CrossRefGoogle Scholar
  2. Boman HG, Wade D, Boman IA, Wåhlin B, Merrifield RB (1989) Antibacterial and antimalarial properties of peptides that are cecropin-melittin hybrids. FEBS Lett 259:103–106CrossRefGoogle Scholar
  3. Brown KL, Hancock RE (2006) Cationic host defense (antimicrobial) peptides. Curr Opin Immunol 18:24–30CrossRefGoogle Scholar
  4. Cheng J, Randall AZ, Sweredoski MJ, Baldi P (2005) SCRATCH: a protein structure and structural feature prediction server. Nucleic Acids Res 33:W72–W76CrossRefGoogle Scholar
  5. Dathe M, Wieprecht T (1999) Structural features of helical antimicrobial peptides: their potential to modulate activity on model membranes and biological cells. Biochim Biophys Acta 1462:71–87CrossRefGoogle Scholar
  6. Deléage G, Clerc FF, Roux B, Gautheron DC (1988) ANTHEPROT: a package for protein sequence analysis using a microcomputer. Comput Appl Biosci 4:351–356PubMedGoogle Scholar
  7. Ferre R, Badosa E, Feliu L, Planas M, Montesinos E, Bardají E (2006) Inhibition of plant-pathogenic bacteria by short synthetic cecropin A-melittin hybrid peptides. Appl Environ Microbiol 72:3302–3308CrossRefGoogle Scholar
  8. Fink J, Merrifield RB, Boman A, Boman HG (1989) The chemical synthesis of cecropin D and an analog with enhanced antibacterial activity. J Biol Chem 264:6260–6267PubMedGoogle Scholar
  9. Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server. In: Walker JM (ed) The Proteomics Protocols Handbook. Humana Press, Totowa, pp 571–607CrossRefGoogle Scholar
  10. Giangaspero A, Sandri L, Tossi A (2001) Amphipathic alpha helical antimicrobial peptides. Eur J Biochem 268:5589–5600CrossRefGoogle Scholar
  11. Huang HW (2000) Action of antimicrobial peptides: two-state model. Biochemistry 39:8347–8352CrossRefGoogle Scholar
  12. Hultmark D, Steiner H, Rasmuson T, Boman HG (1980) Insect immunity. Purification and properties of three inducible bactericidal proteins from hemolymph of immunized pupae of Hyalophora cecropia. Eur J Biochem 106:7–16CrossRefGoogle Scholar
  13. Jin Y, Hammer J, Pate M, Zhang Y, Zhu F, Zmuda E, Blazyk J (2005) Antimicrobial activities and structures of two linear cationic peptide families with various amphipathic beta-sheet and alpha-helical potentials. Antimicrob Agents Chemother 49:4957–4964CrossRefGoogle Scholar
  14. Kneller DG, Cohen FE, Langridge R (1990) Improvements in protein secondary structure prediction by an enhanced neural network. J Mol Biol 214:171–182CrossRefGoogle Scholar
  15. 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
  16. Lee KH, Lee DG, Park Y, Kang DI, Shin SY, Hahm KS, Kim Y (2006) Interactions between the plasma membrane and the antimicrobial peptide HP (2-20) and its analogues derived from Helicobacter pylori. Biochem J 394(Pt 1):105–114CrossRefGoogle Scholar
  17. Lv J, Yin L, Liu T, Wang Y (2007) Synthesis of pseudopeptides based L-tryptophan as a potential antimicrobial agent. Bioorg Med Chem Lett 17:1601–1607CrossRefGoogle Scholar
  18. Marr AK, Gooderham WJ, Hancock RE (2006) Antibacterial peptides for therapeutic use: obstacles and realistic outlook. Curr Opin Pharmacol 5:468–472CrossRefGoogle Scholar
  19. Nomura K, Ferrat G, Nakajima T, Darbon H, Iwashita T, Corzo G (2005) Induction of morphological changes in model lipid membranes and the mechanism of membrane disruption by a large scorpion-derived pore-forming peptide. Biophys J 89:4067–4080CrossRefGoogle Scholar
  20. Park Y, Hahm KS (2005) Effects of N- and C-terminal truncation of HP (2-20) from Helicobacter pylori ribosomal protein L1 (RPL1) on its anti-microbial activity. Biotechnol Lett 27:193–199CrossRefGoogle Scholar
  21. Park CB, Kim HS, Kim SC (1998) Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions. Biochem Biophys Res Commun 244:253–257CrossRefGoogle Scholar
  22. Pütsep K, Brändén CI, Boman HG, Normark S (1999) Antibacterial peptide from H. pylori. Nature 398:671–672CrossRefGoogle Scholar
  23. Rice P, Longden I, Bleasby A (2000) EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet 16:276–277CrossRefGoogle Scholar
  24. 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
  25. 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
  26. Scheller A, Oehlke J, Wiesner B, Dathe M, Krause E, Beyermann M, Melzig M, Bienert M (1999) Structural requirements for cellular uptake of alpha-helical amphipathic peptides. J Pept Sci 5:185–194CrossRefGoogle Scholar
  27. Strøm MB, Haug BE, Rekdal Ø, Skar ML, Stensen W, Svendsen JS (2002) Important structural features of 15-residue lactoferricin derivatives and methods for improvement of antimicrobial activity. Biochem Cell Biol 80:65–74CrossRefGoogle Scholar
  28. Tian ZG, Teng D, Yang YL, Luo J, Feng XJ, Fan Y, Zhang F, Wang JH (2007) Multimerization and fusion expression of bovine lactoferricin derivative LfcinB15-W4,10 in Escherichia coli. Appl Microbiol Biotechnol 75:117–124CrossRefGoogle Scholar
  29. Tossi A, Sandri L, Giangaspero A (2000) Amphipathic, alpha-helical antimicrobial peptides. Biopolymers 55:4–30CrossRefGoogle Scholar
  30. 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
  31. 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

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Zi-gang Tian
    • 1
  • Tian-tang Dong
    • 1
  • Da Teng
    • 1
  • Ya-lin Yang
    • 1
  • Jian-hua Wang
    • 1
    Email author
  1. 1.Gene Engineering Laboratory, Feed Research InstituteChinese Academy of Agricultural SciencesBeijingPeople’s Republic of China

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