Synthesis, characterization, and photoinduced antibacterial activity of porphyrin-type photosensitizers conjugated to the antimicrobial peptide apidaecin 1b

J Med Chem. 2013 Feb 14;56(3):1052-63. doi: 10.1021/jm301509n. Epub 2013 Jan 16.

Abstract

Antimicrobial photodynamic therapy (aPDT) is an emerging treatment for bacterial infections that is becoming increasingly more attractive because of its effectiveness against multi-antibiotic-resistant strains and unlikelihood of inducing bacterial resistance. Among the strategies to enhance the efficacy of PDT against Gram-negative bacteria, the binding to a cationic antimicrobial peptide offers the attractive prospect for improving both the water solubilty and the localization of the photoactive drug in bacteria. In this work we have compared a number of free and apidaecin-conjugated photosensitizers (PSs) differing in structure and charge. Our results indicate that the conjugation of per se ineffective highly hydrophobic PSs to a cationic peptide produces a photosensitizing agent effective against Gram-negative bacteria. Apidaecin cannot improve the phototoxic activity of cationic PSs, which mainly depends on a very high yield of singlet oxygen production in the surroundings of the bacterial outer membrane. Apidaecin-PS conjugates appear most promising for treatment protocols requiring repeated washing after sensitizer delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry*
  • Chromatography, High Pressure Liquid
  • Gram-Negative Bacteria / drug effects
  • Mass Spectrometry
  • Microbial Sensitivity Tests
  • Photochemical Processes
  • Photosensitizing Agents / chemical synthesis*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / chemical synthesis
  • Porphyrins / chemistry
  • Porphyrins / pharmacology
  • Singlet Oxygen / metabolism
  • Spectrometry, Fluorescence
  • Spectrophotometry, Ultraviolet

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Photosensitizing Agents
  • Porphyrins
  • apidaecin
  • Singlet Oxygen