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Chemotherapeutic activity of synthetic antimicrobial peptides: correlation between chemotherapeutic activity and neutrophil-activating activity.

Abstract
The chemotherapeutic activity of three synthetic antibacterial peptides was investigated. KLKLLLLLKLK-NH2 and its D-enantiomer showed significant chemotherapeutic activity in MRSA-infected mice, whereas KLKLLLKLK-NH2, which showed the highest antibacterial activity among them in vitro, was found to have almost no ability to prevent MRSA infection. These results suggest that the antibacterial activity of peptides assessed in vitro does not necessarily correlate with their chemotherapeutic activity. We found that KLKLLLLLKLK-NH2 and its D-enantiomer, but not KLKLLLKLK-NH2, have the ability to activate human neutrophils to produce superoxide, suggesting that the prevention of MRSA infection by these peptides is not simply due to their direct bactericidal activity but to augmentation of the systemic defense mechanism mediated by neutrophils.
AuthorsY Nakajima, J Alvarez-Bravo, J Cho, K Homma, S Kanegasaki, S Natori
JournalFEBS letters (FEBS Lett) Vol. 415 Issue 1 Pg. 64-6 (Sep 22 1997) ISSN: 0014-5793 [Print] NETHERLANDS
PMID9326370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Cytochrome c Group
  • Oligopeptides
  • Superoxides
  • Tetradecanoylphorbol Acetate
Topics
  • Animals
  • Anti-Bacterial Agents (pharmacology)
  • Cytochrome c Group (metabolism)
  • Humans
  • Male
  • Methicillin Resistance
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Neutrophil Activation (drug effects)
  • Neutrophils (drug effects, metabolism)
  • Oligopeptides (chemical synthesis, pharmacology, therapeutic use)
  • Oxidation-Reduction
  • Staphylococcal Infections (drug therapy, microbiology)
  • Staphylococcus aureus (drug effects)
  • Stereoisomerism
  • Superoxides (metabolism)
  • Tetradecanoylphorbol Acetate (pharmacology)

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