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

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.

Antimicrobial activity of RP-1 peptide conjugate with ferrocene group

“…In 5 mmol L -1 of LPC, above the CMC, the peptide increased the content of α-helixes structures [56], showing well-characterized positive and negative bands at 190 nm and 208/222 nm, respectively. The CD spectra in micelles showed aggregation of RP1, considering a characteristic band at 222 nm higher than in 208 nm [56,57]. The absence of a positive band in 190 nm suggests the presence of additional structures.…”

“…In the presence of LPC, a membrane mimetic environment, in a concentration of 1 mmol L -1 , which is below the critical micellar concentration (CMC) [53], RP1 presented a mixture of structures: α-helix, characterized by negative band at 222 nm; and β-sheet structures containing a small shoulder negative band around 215 nm [54,55]. In 5 mmol L -1 of LPC, above the CMC, the peptide increased the content of α-helixes structures [56], showing well-characterized positive and negative bands at 190 nm and 208/222 nm, respectively. The CD spectra in micelles showed aggregation of RP1, considering a characteristic band at 222 nm higher than in 208 nm [56,57].…”

Incorporation of β-Amino Acids Enhances the Antifungal Activity and Selectivity of the Helical Antimicrobial Peptide Aurein 1.2

“…14 Aurein 1.2, a member of the aurein family of AMPs, which also includes aurein 2.2, aurein 3.1, citropin 1.1, citropin 1.1, citropin 1.3, and maculatin 1.1, 17–19 is a 13 residue +1 charged peptide (entry 1 , Table 1) secreted from skin glands of Australian Bell Frogs and exhibits activity against both bacteria and fungi. 14, 20, 21 Aurein 1.2 folds into a helix with hydrophobic and charged residues segregated to different faces (Fig. 1).…”

The importance of cyclic structure for Labaditin on its antimicrobial activity against Staphylococcus aureus

“…At the end of each experiment Triton X-100 (1% v:v) was added for the release of all CF. The percentage of CF leakage was calculated with the equation: 100(Ft−Fo)/(Fmax−Fo), where Ft is the fluorescence at a given time, Fo is the initial fluorescence (before addition of peptide), and Fmax is the maximum fluorescence after addition of Triton X-100 [36][37][38]. All experiments were performed in triplicate.…”