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Antimicrobial activity of leucine‐substituted decoralin analogs with lower hemolytic activity
Author(s) -
Torres Marcelo Der Torossian,
Pedron Cibele Nicolaski,
Lima Julia Aparecida,
Silva Pedro Ismael,
Silva Fernanda Dias,
Oliveira Vani Xavier
Publication year - 2017
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3029
Subject(s) - antimicrobial , amphiphile , chemistry , peptide , leucine , stereochemistry , cationic polymerization , antimicrobial peptides , mechanism of action , mode of action , biochemistry , structure–activity relationship , amino acid , in vitro , organic chemistry , copolymer , polymer
Linear cationic α‐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 α‐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‐NH 2 analog showed similar activity against different microorganisms (c.a. 0.4–0.8 μmol L −1 ), helical structuration, and some hemolytic activity, [Leu] 8 ‐Dec‐NH 2 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 μmol 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 © 2017 European Peptide Society and John Wiley & Sons, Ltd.