Repurposing the scorpion venom peptide VmCT1 into an active peptide against Gram-negative ESKAPE pathogens

Author(s)

Pedron, Cibele Nicolaski ; Araujo, Iris ; da Silva Junior, Pedro Ismael ; da Silva, Fernanda Dias ; Torossian Torres, Marcelo Der ; Oliveira Junior, Vani Xavier

• Document type: Journal article
• Source: BIOORGANIC CHEMISTRY; v. 90, p. 9-pg., 2019-09-01.

Abstract

VmCT1 is a cationic antimicrobial peptide (AMP) from the venom of the scorpion Vaejovis mexicanus. VmCT1 and analogs were designed with single substitutions for verifying the influence of changes in physicochemical features described as important for AMPs antimicrobial and hemolytic activities, as well as their effect on VmCT1 analogs resistance against proteases action. The increase of the net positive charge by the introduction of an arginine residue in positions of the hydrophilic face of the helical structure affected directly the antimicrobial activity. Arg-substituted analogs presented activity against Gram-negative bacteria from the ESKAPE list of pathogens that were not observed for VmCT1. Additionally, peptides with higher net positive charge presented increased antimicrobial activity with values ranging from 0.39 to 12.5 mu mol L-1 against Gram-positive and Gram-negative bacteria and fungi. The phenylalanine substitution by glycine (position 1), and the valine substitution by a proline residue (position 8) led to analogs with lower hemolytic activity (at concentrations 50 and 100 mu mol L-1, respectively). These results revealed that it is possible to modulate the biological activities of VmCT1 derivatives by designing single substituted-analogs as prospective therapeutics against bacteria and fungi. (AU)

• FAPESP's process: 14/04507-5 - Biological applications of new antimicrobial peptides
• Grantee: Marcelo Der Torossian Torres
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/03046-2 - Biologically active peptides against pathogenic microorganisms and cancer cells
• Grantee: Vani Xavier de Oliveira Junior
• Support Opportunities: Regular Research Grants