Banca de QUALIFICAÇÃO: BRUNO AMORIM DO CARMO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : BRUNO AMORIM DO CARMO
DATE: 13/04/2023
TIME: 14:00
LOCAL: Sala Carl Peter von Dietrich
TITLE:

STIGMURIN SCORPION PEPTIDE ANALOGS: STRUCTURAL CHARACTERIZATION, MECHANISM OF ACTION AND IN VIVO BIOLOGICAL ACTIVITY IN NANOSYSTEMS

KEY WORDS:

Tityus stigmurus; scorpion; analog peptides; antimicrobial agents; mechanism of action; nanotechnology; synergism.

PAGES: 102
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Due to the irrational use of antibiotics, several therapeutic limitations have been observed for various microorganisms, which constitutes a serious public health problem, requiring the search for new therapeutic alternatives. The venom of the scorpion Tityus stigmurus is a rich source of biologically active components, including antimicrobial peptides. One of these peptides, called Stigmurin, showed antimicrobial activity and was used as a prototype for obtaining new bioactive molecules. Mutations were made in the structure of Stigmurin to potentiate its activity, generating 31 analogues, where two of these (StigA25 and StigA31) were used in the study. The analogue peptides had an increased antimicrobial activity and spectrum, however, an increase in toxicity was also observed compared to the prototype peptide for erythrocytes. In order to reduce cytotoxicity and increase the serum stability of these peptides, PLGA nanoparticles were used as carriers for these molecules. Thus, the objective of the study was to evaluate the influence of the incorporation of StigA25 and StigA31 peptides into PLGA nanoparticles in reducing toxicity, improving therapeutic efficiency, and characterizing these peptides by NMR. It was possible to obtain stable PLGA nanoparticles, with a high rate of peptide incorporation, with antimicrobial activity equivalent to free peptides, in addition to significantly reducing toxicity. Scanning electron microscopy (SEM) showed that the peptides act through cell lysis of pathogens and that peptides incorporated in nanoparticles act through intracellular mechanisms. Transmission electron microscopy (TEM) showed that both free and nanoparticulate peptides act on the bacterial cell membrane, promoting membrane rupture with consequent release of intracellular content from pathogens. Furthermore, it was possible to characterize and generate three-dimensional structure models of peptides by nuclear magnetic resonance (NMR), obtaining structured models in α-helix.

COMMITTEE MEMBERS:
Presidente - 2195251 - HUGO ALEXANDRE DE OLIVEIRA ROCHA
Interno - 2275890 - MARCELO DE SOUSA DA SILVA
Externa ao Programa - 1569526 - RENATA MENDONÇA ARAUJO - null