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Design of NK-2-derived peptides with improved activity against equine sarcoid cells.

Abstract: Equine sarcoid is a topically accessible model for the evaluation of anticancer peptides acting by physical membrane disruption avoiding the complexity of a systemic application. We aim at evaluating and improving natural peptides for host defence as lead structures, where we focus on the cationic and amphipathic peptide NK-2. Cytotoxicity tests, fluorescence microscopy and a chip-based biosensor, which enabled real-time monitoring of cell metabolism, were applied. Cancer cell killing was dynamic with an initial phase of increased cellular respiration, followed by membrane destruction. NK-2 was substantially improved and shortened. Novel peptides exhibited a fivefold improved activity against sarcoid cells, while haemolysis remained almost unaltered. Similar Zeta potential and similar amount of surface phosphatidylserine of sarcoid and normal skin cells are responsible for a lack of selectivity between these two cell types.
Publication Date: 2013-07-25 PubMed ID: 23893605DOI: 10.1002/psc.2540Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research paper is about the development of enhanced peptides, derived from NK-2, that have shown increased effectiveness against equine sarcoid cells, a common form of skin tumor in horses.

Objective of the Research

  • This research seeks to evaluate and enhance natural peptides for host defence and focuses primarily on the cationic and amphipathic peptide NK-2. The goal is to develop peptides with an ability to disrupt cell membranes of equine sarcoid cells, thereby preventing the progression of this form of skin tumor in horses.

Methodology

  • The research made use of cytotoxicity tests, fluorescence microscopy, and a chip-based biosensor that allowed real-time monitoring of cell metabolism.
  • The efficiency and interaction of these peptides with cancer cells were tested and monitored.

Findings

  • The research found that the revised NK-2 peptides manifested a dynamic killing of cancer cells, involving first an increased cellular respiration phase and then a phase of membrane destruction.
  • The improved NK-2 peptides were substantially more efficient against equine sarcoid cells, with a fivefold improvement in activity and no significant increase in haemolysis.

Lack of Selectivity

  • The research highlighted a challenge of similar Zeta potential and similar amounts of surface phosphatidylserine found in both sarcoid cells and normal skin cells. This similarity makes it difficult to selectively target sarcoid cells without affecting normal cells, potentially leading to unwanted side effects.

Conclusion

  • Despite the challenge of similar Zeta potential in normal skin and sarcoid cells, the study provides a promising path towards the design of effective anticancer peptides against equine sarcoids, paving the way for potential therapeutic interventions for this common equine skin condition.

Cite This Article

APA
Gross S, Wilms D, Krause J, Brezesinski G, Andrä J. (2013). Design of NK-2-derived peptides with improved activity against equine sarcoid cells. J Pept Sci, 19(10), 619-628. https://doi.org/10.1002/psc.2540

Publication

ISSN: 1099-1387
NlmUniqueID: 9506309
Country: England
Language: English
Volume: 19
Issue: 10
Pages: 619-628

Researcher Affiliations

Gross, Stephanie
  • Division of Biophysics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, D-23845, Borstel, Germany.
Wilms, Dominik
    Krause, Jannike
      Brezesinski, Gerald
        Andrä, Jörg

          MeSH Terms

          • Animals
          • Biosensing Techniques
          • Cell Membrane / chemistry
          • Cell Membrane / drug effects
          • Hemolysis
          • Horses / virology
          • Humans
          • Microscopy, Fluorescence
          • Peptides / chemical synthesis
          • Peptides / chemistry
          • Peptides / pharmacology
          • Phosphatidylserines / chemistry
          • Skin Neoplasms / drug therapy
          • Skin Neoplasms / metabolism

          Citations

          This article has been cited 2 times.
          1. Mercurio FA, Di Natale C, Pirone L, Iannitti R, Marasco D, Pedone EM, Palumbo R, Leone M. The Sam-Sam interaction between Ship2 and the EphA2 receptor: design and analysis of peptide inhibitors. Sci Rep 2017 Dec 12;7(1):17474.
            doi: 10.1038/s41598-017-17684-5pubmed: 29234063google scholar: lookup
          2. Maletzki C, Klier U, Marinkovic S, Klar E, Andrä J, Linnebacher M. Host defense peptides for treatment of colorectal carcinoma - a comparative in vitro and in vivo analysis. Oncotarget 2014 Jun 30;5(12):4467-79.
            doi: 10.18632/oncotarget.2039pubmed: 24962950google scholar: lookup