Dados do Trabalho

Título

Biotinylated peptide able to inhibit leishmania internalization inside macrophages: evaluation of its leishmanicidal activity and cytotoxicity.

Introdução

INTRODUCTION: Being part of the neglected tropical diseases listed by the World Health Organization, leishmaniasis affects about 0.7 to 1 million people each year and can be fatal. The disease-causing agent is the parasite of the genus Leishmania spp. and the treatments being used are few; therefore, little therapy options associated with high toxicity of the drugs and inconvenient administration of the medications cause low patient adhesion for this disease. In this way, it is important to find new molecular targets in the parasite to the development of new and more specific drugs that cause less side effects. To find those new molecular targets, PhD Juliane applied a phage display library containing different peptide sequences to investigate compounds that could interact with the parasite surface, resulting in the discovery of peptide A9, which can interact with Leishmania infantum surface and inhibit considerably its entrance to macrophage. Based on these results, peptides A9 and A9SC were synthesized and tested against leishmania and macrophages.

Objetivo (s)

OBJECTIVES: The aim of this work was to synthesize both peptides and evaluate their leishmanicidal activity against promastigote forms of L. infantum as well as their toxicity against differentiated macrophage cells (THP-1).

Material e Métodos

MATERIALS AND METHODS: Peptide synthesis was made by solid-phase method using Wang resin. Peptides purification were performed using high performance liquid chromatography on a C18 reverse phase column. Biological assay for leishmanicidal activity was performed in promastigote form of L. infantum and cytotoxicity was performed in THP-1 cells.

Resultados e Conclusão

RESULTS: Preliminary results showed that both peptides have no activity either against promastigote forms and THP-1 cells. These results were expected since the purpose of A9 is to identify a new molecular target on leishmania surface and not kill the parasite. The viability of the promastigote form was 100% in a concentration of 0.5 mg/mL of A9 and inhibition rate was about 14% in 1.0 mg/mL; therefore, it was not possible to obtain an IC50 value. Peptide A9SC is a linear structure with mostly the same amino acids as A9 and its role is to answer the question if peptide A9 cyclic structure is important to surface interaction. CONCLUSION: A9 interacts with the surface of L. infantum and doesn't kill the parasite, but inhibit macrophage infection as described before; that’s important since it’s better that the leishmania model is intact.

Palavras Chave

Peptide Synthesis; molecular targets; Leishmaniasis