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Engineering of a novel skin secretion peptide of an endemic amphibian of Ecuador (Callimedusa ecuatoriana) into promising antimicrobial molecules.
1, 2 , 1 , 1 , 1, 3 , 1, 4 , * 1
1  Biomolecules Discovery Group, Laboratory of Molecular Biology and Biochemistry, Universidad Regional Amazónica Ikiam, km 7 ½ vía Muyuna, Tena 150150, Ecuador.
2  Life Sciences Faculty, Universidad Regional Amazónica Ikiam, km 7 ½ vía Muyuna, Tena 150150, Ecuador.
3  Laboratory of Microbial Biomolecules, Department of Biochemical and Pharmaceutical Technology, University of São Paulo, São Paulo, Brazil.
4  School of Pharmacy, University of Reading, Reading RG6 6UB, UK.
Academic Editor: Monique Van Hoek (registering DOI)

Amphibian skin secretion has been an important source of broad-spectrum and membrane-targeting antimicrobial peptides, which promise to tackle the antibiotic resistance crisis.Callimedusa ecuatoriana from Ecuador is an example of an unexplored species, that can hold a library of novel chemical scaffolds with antibiotic action. In this study, we report a novel skin peptide (PTR-CE1) identified by molecular cloning of mRNA precursor. We demonstrated that it lacks of antimicrobial activity. So, using the natural sequence of PTR-CE1 as a template, we designed and synthesized two analogs (PTR-CE1a and PTR-CE1b). Both engineered peptides displayed high antibacterial activity, even against the ampicillin-resistant bacterial strains. While PTR-CE1b showed MIC values of 106.5-212.99 mM and less than 10% of damage to red blood cells at 3.02 mM, PTR-CE1a displayed a more potent broad-spectrum effect against all the tested microorganisms, with MIC values of 3.02-12.06 mM, and low hemolytic properties at 6.66 mM. This study highlights the role of the secondary structure for antimicrobial activity and shows how inactive peptides can be useful as a template for the generation of new molecules with high activity and low toxicity.

Keywords: Toxicity; synthetic antimicrobial peptides; amphibian skin secretion peptides; proline; alpha-helix kink.