One of the main advantages of antimicrobial peptides in antibiotic therapy is the reduced chance of resistance development, since these peptides target the phospholipid matrix of the cell membrane. Some of these peptides are also active against Leishmania, which is the causative agent of one of the neglected diseases according to WHO. The current therapies have serious shortcomings related to toxicity, the administration forms and costs. Bioactive peptides from natural sources and their synthetic analogs are investigated to orient structural optimizations that can enhance the therapeutic action and at the same time minimizing toxic or undesirable side effects. To this end studies carried out in model membranes have evidenced the importance of electrostatic and elastic properties of the membrane which are strongly related to the lipid composition of the bilayer. Decoralin is an undecapeptide, which in the C-terminus amidated form exhibits leishmanicidal activity towards the promastigote form of the protozoa and low cytotoxicity. Previous molecular dynamics studies comparing the structures of Decoralin and other leishmanicidal peptides suggest that some structural parameters could be responsible for this activity. This project is the following of FAPESP Process 2014/11877-3, continuing the investigation of new Decoralin analogs, which are structurally relevant according to the molecular dynamics pre-determined parameters. Zeta potential experiments will be carried out to obtain partition constants of these peptides in vesicles that are mimetics of the membranes of amastigotes and infected macrophages, fluorescent probe leakage experiments from the same vesicles will report on the permeabilizing ability of the peptides and circular dichroism spectra will confirm binding and the structural features induced in these environments.
News published in Agência FAPESP Newsletter about the scholarship: