Synthetic antimicrobial peptides: From choice of the best sequences to action mechanisms

Author(s):Show less -

Souza, Pedro F. N. ^[1] ; Marques, Lidyane S. M. ^[1] ; Oliveira, Jose T. A. ^[1] ; Lima, Patricia G. ^[1] ; Dias, Lucas P. ^[1] ; Neto, Nilton A. S. ^[1] ; Lopes, Francisco E. S. ^[1] ; Sousa, Jeanlex S. ^[2] ; Silva, Ayrles F. B. ^[1] ; Caneiro, Romulo F. ^[3] ; Lopes, Jose L. S. ^[4] ; Ramos, V, Marcio ; Freitas, Cleverson D. T. ^[5]

Affiliation

^[1] Univ Fed Ceara, Dept Biochem & Mol Biol, BR-60440554 Fortaleza, Ceara - Brazil

^[2] Univ Fed Ceara, Dept Phys, Fortaleza, Ceara - Brazil

^[3] Univ Fed Ceara, Dept Fishery Engn, Fortaleza, Ceara - Brazil

^[4] Univ Sao Paulo, Inst Phys, Sao Paulo - Brazil

^[5] Ramos, Marcio, V, Univ Fed Ceara, Dept Biochem & Mol Biol, BR-60440554 Fortaleza, Ceara - Brazil

• Document type: Journal article
• Source: Biochimie; v. 175, p. 132-145, AUG 2020.
• Web of Science Citations: 1

Abstract

The emergence of antibiotic-resistant microbes has stimulated research worldwide seeking new biologically active molecules. In this respect, synthetic antimicrobial peptides (SAMPs) have been suggested to overcome this problem. Although there are some online servers that provide putative SAMPs from protein sequences, the choice of the best peptide sequences for further analysis is still difficult. Therefore, the goal of this paper is not to launch a new tool but to provide a friendly workflow to characterize and predict potential SAMPs by employing existing tools. Using this proposed workflow, two peptides (PepGAT and PepKAA) were obtained and extensively characterized. These peptides damaged microbial membranes and cell walls, and induced overproduction of reactive oxygen species (ROS). Both peptides were found to assume random coil secondary structure in aqueous solution, organic solvent, and upon binding to negatively charged lipid systems. Peptides were also able to degrade formed biofilms but not to prevent biofilm formation. PepGAT was not resistant to proteolysis, whereas PepKAA was resistant to pepsin but not to pancreatin. Furthermore, both presented no hemolytic activity against red blood cells, even at a 10-fold higher concentration than the antimicrobial concentration. The pipeline proposed here is an easy way to design new SAMPs for application as alternatives to develop new drugs against human pathogenic microorganisms. (C) 2020 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. (AU)

• FAPESP's process: 18/19546-7 - Molecular mechanisms of the binding, insertion, and orientation of antimicrobial peptides in model membranes
• Grantee: Jose Luiz de Souza Lopes
• Support Opportunities: Regular Research Grants