Enhancing the Activity of Surface Immobilized Antimicrobial Peptides Using Thiol-Mediated Tethering to Poly(ethylene glycol)

Macromol Biosci. 2023 Sep;23(9):e2200411. doi: 10.1002/mabi.202200411. Epub 2023 May 24.

Abstract

Considering the need for versatile surface coatings that can display multiple bioactive signals and chemistries, the use of more novel surface modification methods is starting to emerge. Thiol-mediated conjugation of biomolecules is shown to be quite advantageous for such purposes due to the reactivity and chemoselectivity of thiol functional groups. Herein, the immobilization of poly(ethylene glycol) (PEG) and antimicrobial peptides (AMPs) to silica colloidal particles based on thiol-mediated conjugation techniques, along with an assessment of the antimicrobial potential of the functionalized particles against Pseudomonas aeruginosa and Staphylococcus aureus is investigated. Immobilization of PEG to thiolated Si particles is performed by either a two-step thiol-ene "photo-click" reaction or a "one-pot" thiol-maleimide type conjugation using terminal acrylate or maleimide functional groups, respectively. It is demonstrated that both immobilization methods result in a significant reduction in the number of viable bacterial cells compared to unmodified samples after the designated incubation periods with the PEG-AMP-modified colloidal suspensions. These findings provide a promising outlook for the fabrication of multifunctional surfaces based upon the tethering of PEG and AMPs to colloidal particles through thiol-mediated biocompatible chemistry, which has potential for use as implant coatings or as antibacterial formulations that can be incorporated into wound dressings to prevent or control bacterial infections.

Keywords: antimicrobial peptides; nanoparticles; surface modification; thiol-ene “photo click”; thiol-maleimide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Peptides*
  • Maleimides
  • Polyethylene Glycols* / chemistry
  • Sulfhydryl Compounds / chemistry

Substances

  • Polyethylene Glycols
  • Antimicrobial Peptides
  • Sulfhydryl Compounds
  • Anti-Bacterial Agents
  • Maleimides