Dimerization of aurein 1.2: Effects in structure, antimicrobial activity and aggregation of Cândida albicans cells
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2013-06-01
Autores
Lorenzón, E. N. [UNESP]
Sanches, P. R S [UNESP]
Nogueira, L. G. [UNESP]
Bauab, T. M. [UNESP]
Cilli, Eduardo Maffud [UNESP]
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Resumo
Antimicrobial peptides (AMPs) are a promising solution to face the antibiotic-resistant problem because they display little or no resistance effects. Dimeric analogues of select AMPs have shown pharmacotechnical advantages, making these molecules promising candidates for the development of novel antibiotic agents. Here, we evaluate the effects of dimerization on the structure and biological activity of the AMP aurein 1.2 (AU). AU and the C- and N-terminal dimers, (AU)2K and E(AU)2, respectively, were synthesized by solid-phase peptide synthesis. Circular dichroism spectra indicated that E(AU)2 has a coiled coil structure in water while (AU)2K has an α-helix structure. In contrast, AU displayed typical spectra for disordered structures. In LPC micelles, all peptides acquired a high amount of α-helix structure. Hemolytic and vesicle permeabilization assays showed that AU has a concentration dependence activity, while this effect was less pronounced for dimeric versions, suggesting that dimerization may change the mechanism of action of AU. Notably, the antimicrobial activity against bacteria and yeast decreased with dimerization. However, dimeric peptides promoted the aggregation of C. albicans. The ability to aggregate yeast cells makes dimeric versions of AU attractive candidates to inhibit the adhesion of C. albicans to biological targets and medical devices, preventing disease caused by this fungus. © 2013 Springer-Verlag Wien.
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Antimicrobial peptides, Aurein 1.2, Biological activity, Dimerization, Secondary structure, aurein 1.2, lysophosphatidylcholine, polypeptide antibiotic agent, unclassified drug, alpha helix, amino terminal sequence, antibacterial activity, antifungal activity, antimicrobial activity, Candida albicans, carboxy terminal sequence, cell aggregation, cell permeabilization, cell vacuole, circular dichroism, concentration response, controlled study, dimerization, fungal cell, hemolysis, human, human cell, micelle, microbial adhesion, minimum inhibitory concentration, nonhuman, peptide synthesis, priority journal, protein function, protein structure, solid phase synthesis, Fungi
Como citar
Amino Acids, v. 44, n. 6, p. 1521-1528, 2013.