Abstract (EN):
Although many studies have pointed out the promising role of antimicrobial peptides (AMPs) as therapeutical
agents, their translation into clinical research is being slow due to the limitations intrinsic to their peptide
nature. A number of structural modifications to overcome this problem have been proposed, leading to enhanced
AMP biological lifetimes and therapeutic index. In this work, the interaction between liposomes of different
lipidic composition and a set of lysine Nε-trimethylated analogs of the cecropin A and melittin hybrid peptide,
CA(1-7)M(2-9) [H-KWKLFKKIGAVLKVL-amide], was studied by differential scanning calorimetry (DSC)
and fluorescence spectroscopy. The study was carried out using membrane models for mammalian erythrocytes
(zwitterionic lipids) and for bacteria (mixture of zwitterionic and negatively charged lipids). The results show
that trimethylated peptides interact strongly with negatively charged (bacterial cell model) but not with
zwitterionic (erythrocyte model) liposomes. These results are in agreement with the reduction of cytotoxicity
and ensuing improvement in therapeutic index vs parental CA(1-7)M(2-9) found in a related study. Moreover,
the modified peptides act differently depending on the model membrane used, providing further evidence
that the lipid membrane composition has important implications on AMP membrane activity.
Idioma:
Inglês
Tipo (Avaliação Docente):
Científica
Contacto:
mbastos@fc.up.pt (M. Bastos)