Banca de DEFESA: KARINA AUXILIADORA BRENES ARGUELLO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : KARINA AUXILIADORA BRENES ARGUELLO
DATE: 24/05/2023
TIME: 09:00
LOCAL: A apresentação da defesa ocorrerá virtualmente no endereço: meet.google.com/hwm-irsd-cem
TITLE:

INTERACTIONS BETWEEN PEPTIDE NANOSTRUCTURES AND BIOLOGICAL SYSTEMS AIMING FOR APPLICATION AS BIOACTIVE AGENTS

PAGES: 172
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Físico-Química
SPECIALTY: Química de Interfaces
SUMMARY:

This work aimed to study the interactions in biological systems of two classes of peptidic nanostructures: lipopeptides (LPs) and porphyrin-functionalized β-amyloid peptides. For the first objective, we investigated the antitumor properties of lipopeptides PRWG-C₁₈H₃₇ (1) and PRWG-(C₁₈H₃₇)₂ (2), containing the amino acids L-proline (P), L-arginine (R), L-tryptophan (W), and L-glycine (G), and compared them with materials PK(GCP)WG-C₁₈H₃₇ (3) and PK(GCP)WG-(C₁₈H₃₇)₂ (4), which contain the synthetic amino acid GCP ("Guanidiniocarbonyl pyrrole") in the peptide sequence. Circular dichroism experiments revealed β-sheet structures for all compounds in the series, with a positive particle charge at pH 7. The LPs exhibited concentration- and chemically-dependent cytotoxicity, with deleterious effects on HeLa cells at concentrations below the IC₅₀ in HEK293 cells. This suggests that the harmful effect on HeLa cells is promoted by apoptotic cell death with the loss of mitochondrial membrane potential (ΔΨm).

The second part of the work involved cell viability studies for novel monofunctionalized porphyrins with L,L-diphenylalanine (FF), and different substituents at the meso position. Fluorescence spectra showed the presence of an emission band at 640-660 nm belonging to the Soret band and multiple bands between 700-720 nm, indicating the presence of Q bands. These systems were studied in PBS, revealing a bathochromic spectral shift in the absorption band at 640 nm. The antitumor properties of HeLa cells showed light- and concentration-dependent cytotoxicity, with less than 5% hemolytic effect. When internalization efficiency was analyzed in the dark, FF-porphyrins showed high capture percentages relative to their precursors. However, a necrosis-promoting cell death mechanism was observed once the compounds were irradiated.

Through cytotoxicity assays and mechanism of cell death, both classes of nanostructured systems revealed a harmful effect on tumor cells at concentrations lower than those used in the chemotherapeutic Chlorambucil (CB).

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1544341 - WENDEL ANDRADE ALVES
Membro Titular - Examinador(a) Interno ao Programa - 1768959 - FERNANDO CARLOS GIACOMELLI
Membro Titular - Examinador(a) Externo ao Programa - 1672728 - ANA CAROLINA SANTOS DE SOUZA GALVAO
Membro Titular - Examinador(a) Externo à Instituição - ERICK LEITE BASTOS - USP
Membro Titular - Examinador(a) Externo à Instituição - DIEGO STÉFANI TEODORO MARTINEZ - CNPEM
Membro Suplente - Examinador(a) Interno ao Programa - 1309493 - PEDRO ALVES DA SILVA AUTRETO
Membro Suplente - Examinador(a) Interno ao Programa - 1676364 - JULIANA MARCHI
Membro Suplente - Examinador(a) Externo ao Programa - 1544365 - GISELLE CERCHIARO
Membro Suplente - Examinador(a) Externo à Instituição - EMERSON RODRIGO DA SILVA - UNIFESP