Antimicrobial activity of leucine-substituted decoralin analogs with lower hemolytic activity

Author(s)

Torres, Marcelo Der Torossian ^[1] ; Pedron, Cibele Nicolaski ^[1] ; da Silva Lima, Julia Aparecida ^[1] ; da Silva Junior, Pedro Ismael ^[2] ; da Silvaa, Fernanda Dias ^[1] ; Oliveira Junior, Vani Xavier ^[1]

Affiliation

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Rua Santa Adelia 166, BR-09210170 Santo Andre, SP - Brazil

^[2] Inst Butantan, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF PEPTIDE SCIENCE; v. 23, n. 11, p. 818-823, NOV 2017.
• Web of Science Citations: 6

Abstract

Linear cationic a-helical antimicrobial peptides are promising chemotherapeutics. Most of them act by different mechanisms, making it difficult to microorganisms acquiring resistance. Decoralin is an example of antimicrobial peptide; it was described by Konno et al. and presented activity against microorganisms, but with pronounced hemolytic activity. We synthesized leucine-substituted decoralin analogs designed based on important physicochemical properties, which depend on the maintenance of the amphiphilic alpha-helical tendency of the native molecule. Peptides were synthesized, purified, and characterized, and the conformational studies were performed. The results indicated that the analogs presented both higher therapeutic indexes, but with antagonistic behavior. While {[}Leu](10)-Dec-NH2 analog showed similar activity against different microorganisms (c.a. 0.4-0.8 mu mol L-1), helical structuration, and some hemolytic activity, {[}Leu](8)-Dec-NH2 analog did not tend to helical structure and presented antimicrobial activities two orders higher than the other two peptides analyzed. On the other hand, this analog showed to be the less hemolytic (MHC value = 50.0 mu mol L-1). This approach provided insight for understanding the effects of the leucine substitution in the amphiphilic balance. They led to changes on the conformational tendency, which showed to be important for the mechanism of action and affecting antimicrobial and hemolytic activities. Copyright (C) 2017 European Peptide Society and John Wiley \& Sons, Ltd. (AU)

• FAPESP's process: 14/04507-5 - Biological applications of new antimicrobial peptides
• Grantee: Marcelo Der Torossian Torres
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/12938-6 - Biologically active peptides against pathogenic micro-organisms
• Grantee: Vani Xavier de Oliveira Junior
• Support type: Regular Research Grants
• FAPESP's process: 13/12338-6 - Relationship between structure and activity of microplusin, a copper and iron chelating peptide with antimicrobial activity
• Grantee: Fernanda Dias da Silva
• Support type: Regular Research Grants