Abstract
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.
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The authors are grateful to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação ao Amparo a Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Nível Superior (CAPES) for financial support. EMC is senior researchers of the CNPq, and ENL was the recipient of Ph.D fellowship from CNPq.
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Lorenzón, E.N., Sanches, P.R.S., Nogueira, L.G. et al. Dimerization of aurein 1.2: effects in structure, antimicrobial activity and aggregation of Cândida albicans cells. Amino Acids 44, 1521–1528 (2013). https://doi.org/10.1007/s00726-013-1475-3
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DOI: https://doi.org/10.1007/s00726-013-1475-3