Synthesis and Evaluation of Biological Activity of Antimicrobial--Pro-Proliferative Peptide Conjugates

PLoS One. 2015 Oct 16;10(10):e0140377. doi: 10.1371/journal.pone.0140377. eCollection 2015.

Abstract

Skin represents the largest organ of the human body and plays a crucial role in its protection from the negative impact of the outside environment, maintains its homeostasis, enables sensory interaction and thermoregulation. The traumatized skin tissue undergoes several phenotype switches due to progressive reoxygenation and release of cytokine and growth factors, that activate mechanisms of reparative processes. However, in case of wounds colonized with pathogenic microflora natural regenerative mechanisms become substantially impaired, that could lead to chronic inflammatory states with non-healing skin lesions. Herein, we present the initial results of our studies aimed at the design of bifunctional peptide-based compounds. The chemical approach, that was utilized in this work, was based on the conjugation of antimicrobial peptides with the peptides, that have potential pro-proliferative and/or cytoprotective activity towards human keratinocytes and fibroblasts, in order to obtain antimicrobials with reduced cytotoxicity or compounds that maintain both activities, i.e. inhibit bacterial or fungi growth and activate cell proliferation/migration in in vitro tests. As a result, we obtained a group of peptide conjugates that effectively inhibited the growth of selected bacterial and fungi strains and were able to stimulate proliferation and migration of keratinocytes and fibroblasts under their effective microbicidal concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antimicrobial Cationic Peptides* / chemical synthesis
  • Antimicrobial Cationic Peptides* / chemistry
  • Antimicrobial Cationic Peptides* / pharmacology
  • Bacteria / growth & development*
  • Body Temperature Regulation / drug effects
  • Candida / growth & development*
  • Cell Proliferation / drug effects*
  • Cytoprotection / drug effects
  • Drug Evaluation, Preclinical
  • Female
  • Fibroblasts / metabolism*
  • Fibroblasts / microbiology
  • Humans
  • Male
  • Middle Aged
  • Skin / metabolism*
  • Skin / microbiology

Substances

  • Antimicrobial Cationic Peptides

Grants and funding

This work was supported by Polish National Science Center under the grant number UMO- 2012/04/S/ST5/00074