Conformation of Bradykinin in Relation to Solvent Environment

Abstract

For a small peptide, bradykinin has an unusually large percentage of proline residues in its primary structure. The occurrence of proline in a peptide chain tends to restrict the conformational flexibility of the peptide (1). Bradykinin would therefore be expected to show some degree of ordered structure in solution. Early optical rotatory dispersion (ORD) and circular dichroism (CD) results (2,3), however, suggested that the structure was freely flexible in aqueous solution. Later CD measurements on bradykinin and some of its homologs in aqueous and non-aqueous solvents (4) were interpreted as showing partial intramolecular hydrogenbonding. An 8 → 6 hydrogen-bond across proline⁷ was postulated for bradykinin in aqueous solution, while additional 9 → 7 and 4 → 2 hydrogen-bonds across phenylalanine⁸ and proline³ respectively were postulated in dioxane solution. The model on which Cann’s conclusions are based is an intramolecularly hydrogen-bonded proline derivative in non-aqueous solvents. In non-aqueous solvents the possibility of other intramolecular interactions and solvent interaction with the peptide is minimized. It seems likely therefore, that the model for bradykinin in aqueous solution would be complicated by the possible interactions described above.