Publications (3)4.88 Total impact
Article: Interaction between bradykinin potentiating nonapeptide (BPP9a) and β-cyclodextrin: A structural and thermodynamic study[show abstract] [hide abstract]
ABSTRACT: Herein, we demonstrate the physical and chemical characterizations of the supramolecular complex formed between β-cyclodextrin (βCD) and bradykinin potentiating nonapeptide (BPP9a), an endogenous toxin found in Bothrops jararaca. Circular dichroism results indicate a conformational change in the BPP9a secondary structure upon its complexation with βCD. Nuclear magnetic resonance results, mainly from NOESY experiments, and theoretical calculations showed a favorable interaction between the tryptophan residue of BPP9a and the βCD cavity. Thermodynamic inclusion parameters were investigated by isothermal titration calorimetry, demonstrating that βCD/BPP9a complex formation is an exothermic process that results in a reduction in entropy. Additionally, in vitro degradation study of BPP9a against trypsin (37 °C, pH 7.2) showed higher stability of peptide in presence of βCD. This βCD/BPP9a complex, which presents new chemical properties arising from the peptide inclusion process, may be useful as an antihypertensive drug in oral pharmaceutical formulations.Materials Science and Engineering: C. 01/2011; 32:244-253.
Article: Study of the BPP7a Peptide and its β-Cyclodextrin Complex: Physicochemical Characterization and Complete Sequence Specific NMR Assignments[show abstract] [hide abstract]
ABSTRACT: The BPP7a heptapeptide, p-Glu1Asp2Gly3Pro4Ile5Pro6Pro7, forms an association complex with β-cyclodextrin in a 1:1 molar ratio. The peptide and its complex were characterized by circular dichroism (CD) and isothermal titration calorimetry (ITC), which showed a very weak interaction between the β-cyclodextrin and the peptide. Assignments of all hydrogen resonances of the peptide alone and as a complex were made using 1H nuclear magnetic resonance (NMR) experiments at 400 and 600 MHz. High resolution diffusion ordered spectroscopy (HR-DOSY) experiments were carried out to establish the self-aggregation state of BPP7a. It was also shown that the β-cyclodextrin breaks the molecular clusters leading to complex formation. In addition, the anti-hypertensive activity of the BPP7a/β-cyclodextrin complex was evaluated in spontaneous hypertensive rats (SHR), showing increased activity compared to that of pure BPP7a.Journal of the Brazilian Chemical Society 01/2011; 22:1765-1773. · 1.43 Impact Factor
Article: A Supramolecular Complex between Proteinases and β-Cyclodextrin that Preserves Enzymatic Activity: Physicochemical Characterization[show abstract] [hide abstract]
ABSTRACT: Background: Cyclodextrins are suitable drug delivery systems because of their ability to subtly modify the physical, chemical, and biological properties of guest molecules through labile interactions by formation of inclusion and/or association complexes. Plant cysteine proteinases from Caricaceae and Bromeliaceae are the subject of therapeutic interest, because of their anti-inflammatory, antitumoral, immunogenic, and wound-healing properties.Methods: In this study, we analyzed the association between β-cyclodextrin (βCD) and fraction P1G10 containing the bioactive proteinases from Carica candamarcensis, and described the physicochemical nature of the solid-state self-assembled complexes by Fourier transform infrared (FTIR) spectroscopy, thermogravimetry (TG), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and nuclear magnetic resonance (NMR), as well as in solution by circular dichroism (CD), isothermal titration calorimetry (ITC), and amidase activity.Results and discussion: The physicochemical analyses suggest the formation of a complex between P1G10 and βCD. Higher secondary interactions, namely hydrophobic interactions, hydrogen bonding and van der Waals forces were observed at higher P1G10 : βCD mass ratios. These results provide evidence of the occurrence of strong solid-state supramolecular non-covalent interactions between P1G10 and βCD. Microcalorimetric analysis demonstrates that complexation results in a favorable enthalpic contribution, as has already been described during formation of similar βCD inclusion compounds. The amidase activity of the complex shows that the enzyme activity is not readily available at 24 hours after dissolution of the complex in aqueous buffer; the proteinase becomes biologically active by the second day and remains stable until day 16, when a gradual decrease occurs, with basal activity attained by day 29.Conclusion: The reported results underscore the potential for βCDs as candidates for complexing cysteine proteinases, resulting in supramolecular arrays with sustained proteolytic activity.BioDrugs 12/2005; 20(5):283-291. · 3.44 Impact Factor