Estudo estrutural por 1h-rmn de peptídeos bioativos isolados da secreção cutânea de Hypsiboas Albopunctatus E Leptodactylus Labyrinthicus

• Autor(a) principal: ALVES, Eliane Santana Fernandes
• Data de Publicação: 2012
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/0013000001k8h
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tde/1049
• topic: Ressonância Magnética Nuclear Peptídeos bioativos; Determinação estrutural; Hypsiboas Albopunctatus; Leptodactylus Labyrinthicus; Nuclear Magnetic Resonance; Bioactive peptides; Structural determination; Hypsiboas albopunctatus; Leptodactylus labyrinthicus; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA

Currently, the emergence of fungi, bacteria and viruses resistant to multiple drugs has stimulated interest in the development of antimicrobial peptides with increased therapeutic potential. They generally have properties of extreme importance as antimicrobial selective toxicity, rapid action, specific mechanisms of action and a broad spectrum of antimicrobial action. Many of these features can be found in peptides isolated from frog skin secretions. The main factor that differentiates antimicrobial peptides from other commonly antibiotics used in the conventional therapy is related to their mechanism of action. The driving force for much of the action of antimicrobial peptides is their ability to lysis cell membranes, rapidly killing a broad spectrum of microorganisms. Accordingly, the conformation of the peptide has a great importance in their interaction with the amphiphilic structure of biological membranes. The determination of the tridimensional structure by Nuclear Magnetic Resonance (NMR) technique allows the identification of the spatial position of each amino acid residue and highlighting those that are important for its action and, therefore, could be modified to increase the antimicrobial activity. The study of the three-dimensional structure of peptides in solution is an advantage of the NMR spectroscopy, since it can simulate the physiological environment, by means of surfactants. In this context, the tridimensional structures of two synthetic peptides: ocellatin-P1G16 (GLLDTLKGAAKNVVGGLASKVMEKL-NH2), isolated from the amphibians Leptodactylus labyrinthicus, and hylin a1 (IFGAILPLALGALKNLIK-NH2), isolated from Hypsiboas Albopunctatus, were proposed by NMR. The amphipathic caracter can be visualized by separation of the helix into two distinct sides, one hydrophobic (nonpolar) and the other hydrophilic (polar). The peptide hylin a1 in presence of SDS-d25 showed helical structure between residues Ile-5 to Ile-17 and the peptide ocellatin-P1G16 in SDS-d25 micelles showed a α-helical structure between residues Leu-3 to Lys-24, both are presented in amphipathic α-helix Finally, the molecular analyses of amphipathicity, electrostatic interaction, polarity and exchange hydrogen/deuterium, corroborate the proposed model, suggesting a model of parallel orientation to the peptide hylin a1 and the peptide ocellatin-P1G16 a parallel orientation, but with the cterminal portion immersed in the micelle SDS-d25 between residues Ser-19 to Leu-25, as observed by analyzing exchange hydrogen/deuterium. These structural characteristics make these peptides promising candidates for the development of a new antimicrobial drug.