Evaluation of the Synthetic Multifunctional Peptide Hp-MAP3 Derivative of Temporin-PTa

• Published in: Toxins Vol. 15; no. 1; p. 42
• Main Authors: Silva, Patrícia Souza E, Guindo, Alexya Sandim, Oliveira, Pedro Henrique Cardoso, de Moraes, Luiz Filipe Ramalho Nunes, Boleti, Ana Paula de Araújo, Ferreira, Marcos Antonio, de Oliveira, Caio Fernando Ramalho, Macedo, Maria Ligia Rodrigues, Rossato, Luana, Simionatto, Simone, Migliolo, Ludovico
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05-01-2023; MDPI
• Subjects: Amino Acid Sequence; Amphibian Proteins - pharmacology; Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Bacteria; bacterial resistance; Biofilms; Cancer therapies; Chemotherapy; Circular Dichroism; Construction; Cytotoxicity; Dichroism; Drug development; E coli; Erythrocytes; Escherichia coli; Fungal infections; Fungi; Gram-negative bacteria; Gram-positive bacteria; Humans; Hydrophobicity; Metabolism; Mice; Microbial Sensitivity Tests; Microorganisms; Minimum inhibitory concentration; Mortality; Pathogens; Peptides; Permeability; Plasma; Protein structure; Ranidae; rational design; Residues; Secondary structure; Staphylococcus aureus; Staphylococcus infections; temporins; Toxins; Trifluoroethanol; Tumors; Yeasts; rational design; bacterial resistance; antimicrobial peptides; temporins; fungal infections
• DOI: 10.3390/toxins15010042
• EISSN: 2072-6651

In recent years, antimicrobial peptides isolated from amphibian toxins have gained attention as new multifunctional drugs interacting with different molecular targets. We aimed to rationally design a new peptide from temporin-PTa. Hp-MAP3 (NH
-LLKKVLALLKKVL-COOH), net charge (+4), hydrophobicity (0.69), the content of hydrophobic residues (69%), and hydrophobic moment (0.73). For the construction of the analog peptide, the physicochemical characteristics were reorganized into hydrophilic and hydrophobic residues with the addition of lysines and leucines. The minimum inhibitory concentration was 2.7 to 43 μM against the growth of Gram-negative and positive bacteria, and the potential for biofilm eradication was 173.2 μM. Within 20 min, the peptide Hp-MAP3 (10.8 μM) prompted 100% of the damage to
cells. At 43.3 μM, eliminated 100% of
within 5 min. The effects against yeast species of the
genus ranged from 5.4 to 86.6 μM. Hp-MAP3 presents cytotoxic activity against tumor HeLa at a concentration of 21.6 μM with an IC
of 10.4 µM. Furthermore, the peptide showed hemolytic activity against murine erythrocytes. Structural studies carried out by circular dichroism showed that Hp-MAP3, while in the presence of 50% trifluoroethanol or SDS, an α-helix secondary structure. Finally, Amphipathic Hp-MAP3 building an important model for the design of new multifunctional molecules.