Dimerization of aurein 1.2: effects in structure, antimicrobial activity and aggregation of Cândida albicans cells

• DOI: 10.1007/s00726-013-1475-3
• Publication Date: 2013-03-21T04:07:32Z
• Authors: E. N. Lorenzón; P. R. S. Sanches; L. G. Nogueira; T. M. Bauab; E. M. Cilli
• Keywords: 0301 basic medicine; Protein Conformation; microbial adhesion; antibacterial activity; Anti-Infective Agents; alpha helix; Candida albicans; polypeptide antibiotic agent; Circular Dichroism; protein function; unclassified drug; priority journal; cell permeabilization; Antimicrobial peptides; Dimerization; Staphylococcus aureus; Aurein 1.2; Microbial Sensitivity Tests; minimum inhibitory concentration; Hemolysis; Permeability; lysophosphatidylcholine; Structure-Activity Relationship; 03 medical and health sciences; Secondary structure; micelle; peptide synthesis; Escherichia coli; Humans; controlled study; human; protein structure; Solid-Phase Synthesis Techniques; carboxy terminal sequence; antimicrobial activity; nonhuman; Biological activity; human cell; antifungal activity; fungal cell; Fungi; cell aggregation; 540; circular dichroism; solid phase synthesis; concentration response; amino terminal sequence; cell vacuole; hemolysis; Protein Multimerization; Antimicrobial Cationic Peptides

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.