Synthesis of Peptaibolin, an antimicrobial peptide

• Autor(a) principal: Ribeiro, Ana R. M.
• Data de Publicação: 2020
• Outros Autores: Felgueiras, Helena Prado, Costa, Susana P. G., Pereira-Lima, Sílvia M. M. A.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/74154
• topic: Antimicrobial peptides; Peptide synthesis; Solid-phase approach; Bacteria resistance; Engenharia e Tecnologia::Engenharia dos Materiais

To tackle one of the biggest global health problems, the resistance of microorganisms to antibiotics, a collective effort in the search for more effective agents against bacteria was required. Peptides with antimicrobial activity have been raising much attention as a promising alternative for antibiotics. Peptaibols, for instance, are a family of antimicrobial peptides (AMPs) with great biomedical potential, in which the Peptaibolin can be highlighted. This peptide has gained relevance due to its small amino acids content, only four, and its acetyl group and a phenylalaninol residue (Phol) at the N-terminal and C-terminal, respectively. Here, we report the synthesis of Peptaibolin through Solid Phase Peptide Synthesis assisted by Microwave heating (MW-SPPS) in a pre-loaded Phe-Wang resin. Starting from a loading of 0.51 mmol/g, two syntheses were made, using two different combinations of coupling reagents. The best option was DIC/Oxima, achieving a yield of 50.0%. Proton Nuclear Magnetic Resonance (1H-NMR) studies confirmed the peptide structure, while High Performance Liquid Chromatography (HPLC) verified the peptide purity. The peptide solubility was examined against several combinations of solvents. Peptaibolin was not soluble in water, only in organic solvents or in the combination of both. Antimicrobial testing was conducted using Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa. Minimum inhibitory concentration studies demonstrated the resistance of bacteria to the peptide action and the peptide instability in bacterial growth conditions