Several antimicrobial peptides (AMPs) have been reported in amphibian toxins, as temporin-PTa from Hylarana picturata. The amino acid distribution within a helical structure of AMPs favors the design of new bioactive peptides. Therefore, this work reports the rational design of two new synthetic peptides denominated Hp-MAP1 and Hp-MAP2 derived from temporin-PTa. These peptides present an amphipathic helix with positive charges of +4 and +5, hydrophobic moment (<µH>) of 0.66 and 0.72 and hydrophobicity (<H>) of 0.49 and 0.41, respectively. Hp-MAP1 and Hp-MAP2 displayed in vitro activity against Gram-negative and Gram-positive bacteria from 2.8 to 92 µM, without presenting hemolytic effects. Molecular dynamics simulation suggested that the parent and designed temporin-like peptides lack structural stability in an aqueous solution. By contrast, α-helical structures were predicted in hydrophobic and anionic environments. Additionally, the peptides were simulated on mimetic membranes composed of anionic and neutral phospholipids 1,2-dipalmitoylsn-glycerol-3-phosphatidylglycerol (DPPG-anionic), 1,2-dipalmitoyl-sn-lyco-3 phosphatidylethanolamine (DPPE-neutral). When in contact with DPPG/DPPE (90:10) and DPPG/DPPE (50:50) temporin-PTa, Hp-MAP1 and Hp-MAP2 established interactions guided by hydrogen and saline bounds. Therefore, the findings described here reveal that the optimization of the amphipathic α-helical cationic peptides Hp-MAP1 and Hp-MAP2 enabled the generation of new synthetic antimicrobial agents to combat pathogenic microorganisms.
Keywords: amphibian toxin; amphipathic peptides; antimicrobial peptides; molecular dynamics; rational design.
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