Banca de DEFESA: RAIÇA DOMINIQUE MARIANA GOMES DA COSTA BRAZ

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : RAIÇA DOMINIQUE MARIANA GOMES DA COSTA BRAZ
DATE: 29/10/2025
TIME: 08:00
LOCAL: VIDEOCONFERÊNCIA
TITLE:

TSAP-2 analog peptides: Structural characterization, antimicrobial

activity and association with conventional drugs

KEY WORDS:

TsAP-2; antimicrobial peptides; synthetic analogs; antimicrobial association.

PAGES: 142
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

The growing resistance of pathogens to conventional antimicrobial agents represents a grave

public health issue of global scale. Considering the situation, the need for new therapeutic

alternatives is evident. The development of synthetic analogs based on antimicrobial peptides

(AMPs) found in nature is a demonstrably promising option. TsAP-A16 and TsAP-A41 are

synthetic analogs of TsAP-2, an AMP identified in the venom of the Tityus serrulatus and the

Tityus stigmurus scorpions. In vitro and in vivo, TsAP-2 has shown antimicrobial activity

against Gram-positive bacteria and Candida spp. yeasts. TsAP-A16 and TsAP-A41 were

designed through single replacements on the primary structure of TsAP-2, aiming to obtain

molecules more potent than the native peptide. This study focuses on elucidating

physicochemical and structural aspects of TsAP-A16 and TsAP-A41, as well as assessing the

antimicrobial activity of the peptides in isolation and in combination with conventional drugs,

seeking to appraise the potential contributions of TsAP-A16 and TsAP-A41 to the issue of

antimicrobial resistance. Bioinformatic tools and in vitro methods were employed in the

evaluation of physicochemical characteristics and biological activities of the peptides. In silico

data indicate TsAP-A16 and TsAP-A41 as molecules with structural similarities to TsAP-2, but with

greater affinity for the Gram-positive and Gram-negative membranes, as demonstrated by molecular

dynamics simulations’ results. The analog peptides were obtained through solid phase peptide synthesis

prior to investigation of biological activities. In vitro, the analogs demonstrated broadened action

spectrum in comparison to TsAP-2, acting not only against Candida spp. and Gram-positive bacteria but

Gram-negative strains as well. Preliminary assessment of antifungal molecular mechanisms against

Candida albicans revealed affinity of the analog peptides for ergosterol and indifference toward sorbitol,

suggesting interactions with components of the fungal cell membrane, but not with the cell wall.

Associating the analogs with conventional antibiotics before Staphylococcus aureus e Pseudomonas

aeruginosa revealed synergism in combinations with gentamicin, and additive effect in combinations

with ceftazidime and penicillin. Assays with murine fibroblasts and human red blood cells indicated

concentration-dependent compatibility between the analogs and healthy eukaryotic cells. Furthermore,

in silico predictions of the pharmacokinetic and toxicological profiles suggested that the analogs

would be well tolerated by the human organism. The data obtained in silico and in vitro

corroborate the usefulness of the rational design of molecules derived from scorpion peptides,

indicating the peptides TsAP-A16 and TsAP-A41 as promising candidates for the development

of new antimicrobial agents

COMMITTEE MEMBERS:
Externo à Instituição - DANIEL KEN INAOKA
Presidente - 1544647 - MATHEUS DE FREITAS FERNANDES PEDROSA
Externa à Instituição - TERESINHA GONÇALVES DA SILVA - UFPE