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Amino Acids

, Volume 46, Issue 9, pp 2137–2154 | Cite as

Cell specificity and molecular mechanism of antibacterial and antitumor activities of carboxyl-terminal RWL-tagged antimicrobial peptides

  • N. Dong
  • X. Zhu
  • Y. F. Lv
  • Q. Q. Ma
  • J. G. Jiang
  • A. S. ShanEmail author
Original Article

Abstract

Antimicrobial peptides (AMPs) constitute a diverse class of naturally occurring or synthetic antimicrobial molecules that have potential for use in the treatment of drug-resistant infections. Several undesirable properties of AMPs, however, may ultimately hinder their development as antimicrobial agents. Thus, new synthetic strategies, including primarily the de novo design of AMPs, urgently need to be developed. In this study, a series of peptides, H-(RWL) n (n = 1, 2, 3, 4, or 5), were designed. H represents GLRPKYS from the C-terminal sequence of AvBD-4. Our results showed that these RWL-tagged peptides can kill not only bacteria but also human hepatocellular carcinoma HepG2 cells. However, the peptide tagged with two repeats of RWL (GW13) showed less affinity to human embryonic lung fibroblast MRC-5 cells or human red blood cells (hRBCs) than HepG2 cells. These results demonstrated that GW13, with high amphiphilicity, exerted great selectivity toward bacteria and cancer cells, sparing host mammalian cells. The mechanism of action against bacteria was elucidated through combined studies of scanning electron microscopy (SEM) and fluorescence assays, showing that the peptide possessed membrane-lytic activities against microbial cells. The fluorescence assays illustrated that GW13 induced apoptosis in HepG2 cells. The cell morphology of HepG2 cells, observed by SEM, further illustrated that GW13 causes cell death by damaging the cell membrane. Our results indicate that GW13 has considerable potential for future development as an antimicrobial and antitumor agent.

Keywords

Antimicrobial peptides Cell specificity Membrane permeability Hemolysis Apoptosis 

Abbreviations

AMP

Antimicrobial peptide

MIC

Minimum inhibitory concentration

MHC

Minimal hemolytic concentration

CD

Circular dichroism

SDS

Sodium dodecyl sulfate

PC

Phosphatidylcholine

PE

Phosphatidylethanolamine

PG

Phosphatidylglycerol

MH

Mueller–Hinton

PI

Propidium iodide

CCCP

Carbonyl cyanide m-chlorophenylhydrazone

Notes

Acknowledgments

This work was supported financially by the National Basic Research Program (2012CB124703), the National Natural Science Foundation of China (31272453), the China Agriculture Research System (CARS-36), the Postgraduate Innovative Research Projects of Heilongjiang Province (YJSCX2012-004HLJ), and the Open Projects of Key Laboratory of Feed Science, College of Heilongjiang Province (yy-2012-03).

Conflict of interest

We have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled: “Cell specificity and molecular mechanism of antibacterial and antitumor activities of carboxyl-terminal RWL-tagged antimicrobial peptides”.

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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • N. Dong
    • 1
  • X. Zhu
    • 1
  • Y. F. Lv
    • 1
  • Q. Q. Ma
    • 1
  • J. G. Jiang
    • 2
  • A. S. Shan
    • 1
    Email author
  1. 1.Laboratory of Molecular Nutrition and Immunity, Institute of Animal NutritionNortheast Agricultural UniversityHarbinChina
  2. 2.State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunChina

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