Synthesis, Spectroscopic, and Photophysical Characterization and Photosensitizing Activity toward Prokaryotic and Eukaryotic Cells of Porphyrin-Magainin and -Buforin Conjugates

Abstract

Cationic antimicrobial peptides (CAMPs) and photodynamic therapy (PDT) are attractive tools to combat infectious diseases and to stem further development of antibiotic resistance. In an attempt to increase the efficiency of bacteria inactivation, we conjugated a PDT photosensitizer, cationic or neutral porphyrin, to a CAMP, buforin or magainin. The neutral and hydrophobic porphyrin, which is not photoactive per se against Gram-negative bacteria, efficiently photoinactivated Escherichia coli after conjugation to either buforin or magainin. Conjugation to magainin resulted in the considerable strengthening of the cationic and hydrophilic porphyrin's interaction with the bacterial cells, as shown by the higher bacteria photoinactivation activity retained after washing the bacterial suspension. The porphyrin-peptide conjugates also exhibited strong interaction capability as well as photoactivity toward eukaryotic cells, namely, human fibroblasts. These findings suggest that these CAMPs have the potential to carry drugs and other types of cargo inside mammalian cells similar to cell-penetrating peptides.

Strategies for optimizing the delivery to tumors of macrocyclic photosensitizers used in photodynamic therapy (PDT)

“…Recently we have reported that some small cationic peptides that had been previously investigated for their antimicrobial activity can be also used as carriers for enhancing the cellular uptake of tetrapyrrolic PSs [4,86]. We conjugated a hydrophobic meso-tetraphenylporphyrin (cTPP), functionalized with a carboxylic group, to the N-terminus of apidaecin 1b (Api), magainin (Mag) and buforin (Buf).…”

“…Different types of prokaryotic and eukaryotic cells can be killed with this modality provided that the PS has been taken up by the cell or is located in close proximity for allowing the generated ROS to interact with cellular substrates susceptible of photo-oxidative modifications [3,4]. Because of its general or nonspecific mechanism of action, PDT is often proposed for the treatment of various kind of pathological situations.…”

Current Developments in Using MESO-(TETRA) Substituted Porphyrins for PDT

“…27). 101 The porphyrin-magainin conjugate increased the binding of the cationic and hydrophilic porphyrins with bacterial cells as indicated by the high photo-inactivation which was retained after Current developments in using meso-(Tetra)substituted porphyrins for PDT 39 washing the bacterial suspension. Solid-phase synthesis and more complex reaction conditions have also found applications in this field.…”

Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections

“…Anionic and neutral porphyrins are generally not recommended for targeting Gram-negative bacteria due to their poor binding efficacy. However, the association of anionic and neutral porphyrins with Gram-negative bacteria can be considerably improved by the conjugation of cationic antimicrobial peptides (CAMPs) or cell penetrating peptides (CPPs) such as apidaecin [42,43], Tat [44], buforin, or magainin [45] to the PS. These PS-peptide conjugates effectively photosensitized E. coli and induced considerable cell death following APDT compared to unconjugated PS.…”

“…Cationic antimicrobial peptides (CAMPs) such as buforin, magainin, and apidaecin are useful antimicrobial peptides that may be conjugated to PSs to improve PS-cell association or intracellular PS delivery [43,45]. The peptides possess bacterial lytic properties and have particular affinity for Gram-negative bacteria.…”