Banca de QUALIFICAÇÃO: MATEUS FARIAS DE SOUZA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : MATEUS FARIAS DE SOUZA
DATE: 20/09/2023
TIME: 14:30
LOCAL: Sala Virtual Remota (Microsoft Teams) https://bit.ly/Qualif_Msc_MateusSouza_PGBIOEXP
TITLE:

Trypanothione reductase of Leishmania braziliensis as a molecular target for the prospecting of new inhibitors: In vitro and in silico evaluation of Gyroxin and Convulxin from Crotalus durissus terrificus as inhibitors

KEY WORDS:

Trypanothione reductase. Leishmania braziliensis. Snake toxins. Convulxin. Gyroxin.

PAGES: 75
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Trypanothione reductase (TR) is a validated molecular target for the development of new inhibitors for the treatment of diseases caused by Trypanosomatids. On another note, snake venom toxins, due to their structural and functional diversity, are important sources of bioactive molecules for the development of new drugs, including the treatment of diseases like Leishmaniasis. In this context, the present study aims to analyze the interaction of toxins (gyroxin and convulxin from Crotalus durissus terrificus) with the trypanothione reductase of L. braziliensis (TRLb) through in silico models and evaluate their inhibition through in vitro models. To achieve this, molecular docking between TRLb and toxins was performed using the ClusPro2.0 tool. Subsequently, the TRLb gene was inserted into the pET 28(a+) vector and expressed in E. coli. The relative molecular mass and isoelectric point were determined through 12.5% monodimensional and bidimensional SDS-PAGE, and enzymatic activity was assessed using colorimetric methods. The venom of Crotalus durissus terrificus was obtained from the venom bank of LABIOPROT-FIOCRUZ-RO. This venom was fractionated through molecular exclusion chromatography, and the lyophilized fractions were stored at a temperature of -20ºC. As results, in silico assays indicated that convulxin is capable of interacting with the NADPH site and gyroxin is located near the catalytic site of the enzyme, opening possibilities for the development of new research in the field. The TRLb was obtained with a high degree of purity and preserved catalytic activity, showing molecular mass and isoelectric point consistent with those described in the literature. The fractionation of the C.d.t venom resulted in 5 fractions enriched with the toxins of interest using chromatographic profiling and molecular mass as parameters.

COMMITTEE MEMBERS:
Externa à Instituição - RENATA RODRIGUES SANTOS
Externo à Instituição - DANIEL SOL SOL DE MEDEIROS - IFRO
Presidente - 1522184 - LEONARDO DE AZEVEDO CALDERON