Interaction between bradykinin potentiating nonapeptide (BPP9a) and β-cyclodextrin: A structural and thermodynamic study

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.

Figure optionsDownload as PowerPoint slideHighlights
► Cd and NMR showed evidences for the existence of more than one structure in solution.
► Complexation with βCD reduces the conformational rigidity of the peptide.
► βCD cavity recognize Trp and/or Pro segments of BPP9a.
► Interactions involving disaggregation of BPP9a assemblies and binding with βCD.