Effects of Conjugation of Ferrocene and Gallic Acid On desCys11/Lys12/Lys13-(p-BthTX-I)2K Peptide: Structure, Permeabilization and Antibacterial Activity

• Main Author: Pereira, Marina Rodrigues [UNESP]
• Publication Date: 2023
• Other Authors: Rodrigues, Vanessa Dos Santos [UNESP], de Oliveira, Warlley Campos [UNESP], Duque, Cristiane [UNESP], da Silva, Benise Ferreira, Santos-Filho, Norival Alves [UNESP], Carneiro, Victor Alves, Lorenzón, Esteban Nicolás, Cilli, Eduardo Maffud [UNESP]
• Format: Article
• Language: eng
• Source: Repositório Institucional da UNESP
• Download full: http://dx.doi.org/10.2174/0929866530666230721112129; https://hdl.handle.net/11449/300010
• topic: AMPs; Antibiotics; antimicrobial peptides; bioconjugate; S. aureus; vesicle permeabilization

Background: Antimicrobial resistance is an emerging global health challenge that has led researchers to study alternatives to conventional antibiotics. A promising alternative is antimi-crobial peptides (AMPs), produced as the first line of defense by almost all living organisms. To improve its biological activity, the conjugation of AMPs is a promising approach. Objective: In this study, we evaluated the N-terminal conjugation of p-Bt (a peptide derived from Bothrops Jararacuçu`s venom) with ferrocene (Fc) and gallic acid (GA). Acetylated and linear ver-sions of p-Bt were also synthesized to evaluate the importance of N-terminal charge and dimeric structure. Methods: The compounds were obtained using solid-phase peptide synthesis. Circular dichroism, vesicle permeabilization, antimicrobial activity, and cytotoxicity studies were conducted. Results: No increase in antibacterial activity against Escherichia coli was observed by adding ei-ther Fc or GA to p-Bt. However, Fc-p-Bt and GA-p-Bt exhibited improved activity against Staphy-lococcus aureus. No cytotoxicity upon fibroblast was observed for GA-p-Bt. On the other hand, conjugation with Fc increased cytotoxicity. This toxicity may be related to the membrane permeabi-lization capacity of this bioconjugate, which showed the highest carboxyfluorescein leakage in vesicle permeabilization experiments. Conclusion: Considering these observations, our findings highlight the importance of adding bioac-tive organic compounds in the N-terminal position as a tool to modulate the activity of AMPs.