Estudo por ressonância magnética nuclear da estrutura e interação de novos protótipos de biofármacos antimicrobianos
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2016-04-18
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Universidade Federal de Goiás
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Antimicrobial peptides are gaining high importance in the pharmaceutical sector given its high affinity and selectivity to interact with targets, and its low toxicity profile. The increase in the number of peptides screened in clinical trials is a significant triumph for structural biology, considering the search for peptides that meet the required criteria in terms of cost, stability, long half-life and bioavailability.
This research is best performed with a good understanding of the mechanisms of action, dynamics and biomolecules kinetics. Nuclear magnetic resonance spectroscopy (NMR) plays an important role in this context, since it provides informations about the interactions in target binding solution of biologically active molecules. Thus, this study aims to observe the intramolecular interactions of peptides clavanin A, Cm-p1 and [Phe3]Cm-p1. The clavanin peptide is found in tunicate blood cells Styela clava, and presents a broad spectrum of activity against Gram-positive and Gram-negative bacteria, and against several kinds of fungi. The Cm-p1 peptide can be extracted from the crude extract of the marine snail Cenchritis muricatus, and shows activity against yeasts and filamentous fungi. The peptide [Phe3]Cm-p1 corresponds to Cm-p1 peptide modified with a change in residue position 3. Circular dichroism spectroscopy was used in the observation of secondary structure of peptide, and the informations provided by NMR were used in the studies of molecular modeling.
The clavanin peptide in the presence of TFE (2,2,2-trifluoroethanol), presented a amphipathic alpha-helices from Phe-2 to Val-22 residues. The Cm-p1 peptide was structured in α-helix, short amphipathic, in the presence of micelles of SDS-d25 between Arg-2 and Ile-6 residues. The peptide [Phe3]Cm-p1 in the presence of micelles SDS-d25 (sodium dodecyl sulfate) is structured between Arg-2 and Gln-9, showing that the addition of a hydrophobic residue in position 3 provided a greater interaction peptide-micelle, as noted by the smaller diffusion of the peptide [Phe3]Cm-p1 relative to Cm-p1 peptide. All the obtained structures showed good quality and geometry, as revealed by the validation study.
NMR spectroscopy provided information about the intramolecular interactions of peptides clavanin A, Cm-p1 and [Phe3]Cm-p1. It was possible to assign the residues which were important in the interactions between the peptides and the environment. This knowledge is essential in the development of new drugs.
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ALVES, E. S. F. Estudo por ressonância magnética nuclear da estrutura e interação de novos protótipos de biofármacos antimicrobianos. 2016. 155 f. Tese (Doutorado em Química) - Universidade Federal de Goiás, Goiânia, 2016.