Isolation and functional and structural characterization of antitumor peptide from snake venoms of the Bothrops genre

Abstract

Leukemia is a malignant disease of white blood cells, usually of unknown origin, whose main characteristic is the accumulation of abnormal young cells in the bone marrow, which replace normal blood cells. To evaluate new alternative therapies for the treatment of this disease, that affects thousands of individuals every year, this research project aims to evaluate the antitumor activity of peptides isolated from the venom of Bothrops snakes. Snake venoms are rich "libraries" of bioactive molecules with the potential to treat physiological disorders. Among these compounds, peptides stand out that are functionally and structurally well characterized, presenting high selectivity and specificity to human cell receptors, which offers significant advantages in cancer therapy. Thus, samples of venomous snakes of the Bothrops genus will be filtered in Vivaspin, following molecular exclusion chromatography and reverse phase chromatography on HPLC, in order to isolate the peptides to have their activity tested. The fractions and peptides obtained will be tested against a monocyte cell line derived from the peripheral blood of a patient with acute monocytic leukemia (THP-1), a type of AML (M5). The cytotoxic activity will be evaluated using the colorimetric method of metiltetrazolium (MTT) and, from the results obtained, the bioactive native peptide with biotechnological potential will be selected which will be synthesized for later structural and functional evaluation in vitro. The results obtained in the present project seek to understand the relation between structure-function of peptides from venoms in biological systems, contributing to the development of new drugs with potential therapeutic application in the treatment of leukemia. (AU)