Abstract
Antimicrobial peptides (AMPs) isolated from several organisms have been receiving much attention due to some specific features that allow them to interact with, bind to, and disrupt cell membranes. The aim of this paper was to study the interactions between a membrane mimetic and the cationic AMP Ctx(Ile21)-Ha as well as analogues containing the paramagnetic amino acid 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) incorporated at residue positions n = 0, 2, and 13. Circular dichroism studies showed that the peptides, except for [TOAC13]Ctx(Ile21)-Ha, are unstructured in aqueous solution but acquire different amounts of α-helical secondary structure in the presence of trifluorethanol and lysophosphocholine micelles. Fluorescence experiments indicated that all peptides were able to interact with LPC micelles. In addition, Ctx(Ile21)-Ha and [TOAC13]Ctx(Ile21)-Ha peptides presented similar water accessibility for the Trp residue located near the N-terminal sequence. Electron spin resonance experiments showed two spectral components for [TOAC0]Ctx(Ile21)-Ha, which are most likely due to two membrane-bound peptide conformations. In contrast, TOAC2 and TOAC13 derivatives presented a single spectral component corresponding to a strong immobilization of the probe. Thus, our findings allowed the description of the peptide topology in the membrane mimetic, where the N-terminal region is in dynamic equilibrium between an ordered, membrane-bound conformation and a disordered, mobile conformation; position 2 is most likely situated in the lipid polar head group region, and residue 13 is fully inserted into the hydrophobic core of the membrane.
Highlights
The fight against bacterial infections has become a major public health problem
Cationic antimicrobial peptides [2,3] are promising. cationic antimicrobial peptides (cAMPs) are characterized by the high occurrence of basic amino acids, a considerable percentage of hydrophobic amino acids and a greater tendency to adopt amphipathic ahelical structures
Three analogues containing the paramagnetic amino acid tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) strategically inserted in different positions of the sequence (Table I) were designed
Summary
The fight against bacterial infections has become a major public health problem. Classical antibiotics commercialized nowadays are not always an efficient therapy due to the development of bacterial resistance [1]. The search for new molecules from different sources, such as microbes, plants, amphibians, insects and mammals, is an interesting alternative strategy In this context, cationic antimicrobial peptides (cAMPs) [2,3] are promising. Castro’s group has isolated a cationic antimicrobial peptide from the skin secretion of an arboreal South American frog, Hypsiboas albopunctatus [6] This peptide – called Ctx(Ile21)-Ha (ceratotoxin-like peptide from Hypsiboas albopunctatus) – presents the following primary structure: Gly-Trp-Leu-Asp-Val-Ala-Lys-LysIle-Gly-Lys-Ala-Ala-Phe-Asn-Val-Ala-Lys-Asn-Phe-(Ile/Leu) [7]. This sequence does not have similarity with other sequences found in amphibians, but it does have homology with the ceratotoxins peptide family, ceratotoxin A [8]. Due to the increase of the resistance to conventional drugs, analogues of this peptide could be used as new candidates for antimicrobial therapy, which requires the elucidation of its mode of action
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