The effect of lysine substitutions in the biological activities of the scorpion venom peptide VmCT1

Author(s)

Pedron, Cibele Nicolaski ^[1] ; de Oliveira, Cyntia Silva ^[2] ; da Silva, Adriana Farias ^{[1, 2]} ; Andrade, Gislaine Patricia ^[1] ; da Silva Pinhal, Maria Aparecida ^[2] ; Cerchiaro, Giselle ^[1] ; da Silva Junior, Pedro Ismael ^[3] ; da Silva, Fernanda Dias ^[1] ; Torresd, Marcelo Der Torossian ^{[4, 5]} ; Oliveira, Vani Xavier ^{[1, 2]}

Affiliation

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil

^[2] Univ Fed Sao Paulo, BR-04044020 Sao Paulo, SP - Brazil

^[3] Inst Butantan, BR-05503900 Sao Paulo, SP - Brazil

^[4] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 - USA

^[5] Univ Penn, Perelman Sch Med Chem, Dept Psychiat & Microbiol, Philadelphia, PA 19104 - USA

• Document type: Journal article
• Source: European Journal of Pharmaceutical Sciences; v. 136, AUG 1 2019.
• Web of Science Citations: 0

Abstract

Antimicrobial peptides (AMPs) are biologically active molecules with a broad-spectrum activity against a myriad of microorganisms. Aside from their antimicrobial functions, AMPs present physicochemical and structural properties that allow them to exert activity against other kind of cells, such as cancer cells. VmCT1 is a potent cationic amphipathic AMP from the venom of the scorpion Vaejovis mexicanus. In this study, we designed lysine-substituted VmCT1 analogs for verifying the influence of changes in the net positive charge on biological activities. The increase in the net positive charge caused by lysine substitutions in the hydrophilic portion, led to higher antimicrobial activity values (0.1-6.3 mu mol L-1) than VmCT1 (0.8-50 mu mol L-1) and higher activity against mammary cancer cells MCF-7 (6.3-12.5 mu mol L-1) than VmCT1 (12.5 mu mol L-1). Contrarily, when lysine-substitutions were made at the hydrophobic portion of the helical projection, the activity values decreased. However, the lysine-substitution at the center of the hydrophobic face led to the generation of an analog with antiplasmodial activity at the same concentration presented by VmCT1 (0.8 mu mol L-1). In this study, we demonstrated that it is possible to modulate biological activities and cytotoxicity of VmCT1 peptides by increasing their net positive charge using lysine residues, thus creating alternatives for standard-of-care therapeutics against different types of microorganisms and MCF-7 human breast cancer cells. (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