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Improved smallest peptides based on positive charge increase of the γ-core motif from D1 and their mechanism of action against Candida species

Authors Mello ÉO, Taveira GB, de Oliveira Carvalho A, Gomes VM

Received 28 September 2018

Accepted for publication 15 December 2018

Published 9 January 2019 Volume 2019:14 Pages 407—420


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster

Érica de Oliveira Mello, Gabriel Bonan Taveira, André de Oliveira Carvalho, Valdirene Moreira Gomes

Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadualdo Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro, Brazil

 Plant defensins have a hallmark γ-core motif (GXCX3-9C) that is related to their antimicrobial properties. The aim of this work was to design synthetic peptides based on the region corresponding to the D1 defensin γ-core that are the smallest amino acid sequences that bear the strongest biological activity.
Methods: We made rational substitutions of negatively charged amino acid residues with positively charged ones, and the reduction in length in the selected D1 γ-core sequence to verify whether the increased net positive charges and shortened length are related to the increase in antifungal activity. Herein, we opted to evaluate the action mechanism of γ33-41D1++ peptide due to its significant inhibitory effect on tested yeasts. In addition, it is the smallest construct comprising only nine amino acid residues, giving it a better possibility to be a prototype for designing a new antifungal drug, with lower costs to the pharmaceutical industry while still maintaining the strongest antimicrobial properties.
 The γ33-41D1++ peptide caused the most toxic effects in the yeast Candida buinensis, leading to membrane permeabilization, viability loss, endogenous reactive oxygen species increase, the activation of metacaspase, and the loss of mitochondrial functionality, suggesting that this peptide triggers cell death via apoptosis.
We observed that the antifungal activity of D1 is not strictly localized in the structural domain, which comprises the γ-core region and that the increase in the net positive charge is directly related to the increase in antifungal activity.

defensin, antimicrobial peptide, cationic, mechanism of action

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