A synthetic peptide derived of the β 2 –β 3 loop of the plant defensin from Vigna unguiculata seeds induces Leishmania amazonensis apoptosis-like cell death

For medical use of proteins and peptide-based drugs, it is desirable to have small biologically active sequences because they improve stability, reduce side effects, and production costs. Several plant defensins have their biological activities imparted by a sequence named γ-core. Vu -Def, a Vigna unguiculata defensin, has activity against Leishmania amazonensis , which is one etiological agent of leishmaniasis and for which new drugs are needed. Our intention was to understand if the region comprising the Vu -Def γ-core is responsible for the biological activity against L . amazonensis and to unveil its mechanism of action. Different microbiological assays with L . a mazonensis in the presence of the synthetic peptide A 36 , 42 , 44 γ 32-46 Vu -Def were done, as well as ultrastructural and fluorescent analyses. A 36 , 42 , 44 γ 32-46 Vu -Def showed biological activity similar to Vu -Def. A 36 , 42 , 44 γ 32-46 Vu -Def (74 µM) caused 97% inhibition of L . amazonensis culture and parasites were unable to regrow in fresh medium. The cells of the treated parasites showed morphological alterations by ultrastructural analysis and fluorescent labelings that corroborate with the data of the organelles alterations. The general significance of our work is based on the description of a small synthetic peptide, A 36 , 42 , 44 γ 32-46 Vu -Def, which has activity on L . amazonensis and that the interaction between A 36 , 42 , 44 γ 32-46 Vu -Def- L . amazonensis results in parasite inhibition by the activation of an apoptotic-like cell death pathway.