Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Influences of Hinge Region of a Systhetic Antimicrobial Peptide, Cecropin A(1-13)-Melittin(1-13) Hybrid on Antibiotic Activity

  • Published : 1999.09.20
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Abstract

A synthetic cecropin A(1-13)-melittin(1-13) [CA-ME] hybrid peptide was known to be an antimicrobial peptide having strong antibacterial, antifungal and antitumor activity with minimal cytotoxic effect against human erythrocyte. Analogues were synthesized to investigate the influences of the flexible hinge region of CA-ME on the antibiotic activity. Antibiotic activity of the peptides was measured by the growth inhibition against bac-terial, fungal and tumor cells and vesicle-aggregating or disrupting activity. The deletion of Gln-Gly-Ile (P1) or Gly-Gln-Gly-Ile-Gly (P3) from CA-ME brought about a significant decrease on the antibiotic activities. In contrast, Gly-Ile-Gly deletion (P2) from CA-ME or Pro insertion (P5) instead of Gly-Gln-Gly-Ile-Gly of CA-ME retained antibiotic activity. This result indicated that the flexible hinge or β-bend structure provided by Gly-Gln-Gly-Ile-Gly, Gln-Gly, or Pro in the central region of the peptides is requisite for its effective antibiotic activity and may facilitate easily the hydrophobic C-terminal region of the peptide to penetrate the lipid bilayers of the target cell membrane. In contrast, P4 and P6 with Gly-Gln-Gly-Pro-Gly or Gly-Gln-Pro in the central region of the peptide caused a drastic reduction on the antibiotic activities. This result suggested that the con-secutive β-bend structure provided by Gly-Gln-Gly-Pro-Gly or Gly-Gln-Pro in the central hinge region of the peptide seems to interrupt the ion channel/pore formation on the target cell membranes.

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References

  1. Cell v.65 Boman, H. G.
  2. Annu. Rev. Immunol. v.13 Boman, H. G.
  3. Cell v.65 Boman, H. G.
  4. Science v.264 Gabay, J. E.
  5. Biopolymers(Pept. Sci.) v.37 Malov, W. L.;Kari, U. P.
  6. Lancet v.349 Hancock, R. E.
  7. J. Antimicrobial Agents v.9 Miyasaki, K. T.;Lehrer, R. I.
  8. Annu. Rev. Biochem. v.59 Bevins, C. L.;Zasloff, M.
  9. Biochemistry v.34 Matsuzaki, K.;Sugishita, K.;Fujii, N.;Miyajima, K.
  10. Nature v.292 Steiner, H.;Hultmark, D.;Engstrom, A.;Bennich, H.;Boman, H. G.
  11. Proc. Natl. Acad. Sci. USA v.86 Lee, J. Y.;Boman, A.;Sun, C.;Andersson, M.;Jornvall, H.;Mutt, V.;Boman, H. G.
  12. J. Membr. Biol. v.87 Tosteson, M. T.;Holmes, S. J.;Razin, M.;Tosteson, D. C.
  13. FEBS Lett. v.259 Boman, H. G.;Wade, D.;Boman, A.;Wahlin, B.;Meriffield, R. B.
  14. FEBS Lett. v.296 Andreu, D.;Ubach, J.;Boman, A.;Wahlin, D.;Wade, D.;Merrifield, R. B.;Boman, H. G.
  15. Int. Peptide Protein Res. v.40 Wade, D.;Andreu, D.;Mitchell, S. A.;Silveira, A. M. V.;Boman, A.;Boman, H. G.;Merrifield, R. B.
  16. J. Peptide Res. v.53 Shin, S. Y.;Kang, J. H.;Hahm, K.-S.
  17. FEBS Lett. v.137 Steiner, H.
  18. Biochemistry v.21 Merrifield, R. B.;Vizioli, L. D.;Boman, H. G.
  19. Biochemistry v.27 Holak, T. A.;Engstrom, A.;Kraulis, P. J.;Lindeberg, G.;Bennich, H.;Jones, T. A.;Gronenborn, A. M.;Clore, G. M.
  20. Science v.232 Merrifield, R. B.
  21. Biochim. Biophys. Acta. v.689 Ohki, S.
  22. Biochim. Biophys. Acta v.732 Duzgunes, N.;Wilschut, J.;Hong, K.;Fraley, R.;Perry, C.;Friend, D.;James, T. L.;Paphadjopoulos, P.
  23. Biochemistry v.13 Chen, Y.-H.;Yang, J. T.;Chau, K. H.
  24. Eur. J. Biochem. v.199 Sipos, D.;Chandrasekhar, K.;Arvidsson, K.;Engstrom, H.;Ehrenberg, A.
  25. Cancer. Res. v.51 Utsugi, T.;Schroit, A. J.;Connor, J.;Bucana, C. D.;Filder, I. J.
  26. Biochim. Biophys. Acta v.1336 Chan, H. M.;Wang, W.;Simth, D.;Chan, S. C.