Hydroxyproline Analogs of Bradykinin: Biological Activities and Solution Structures

Abstract

Our previous studies by circular dichroism (CD) indicate that bradykinin, Lys-bradykinin, Met-Lys-bradykinin, and Polistes kinin exist in solution as disordered chains (1,2), and examination of the CD spectra in the 250-300 nm range yields no evidence of intraor inter-molecular association of the phenylalanine residues. In brief, spectra of all of the biologically active analogs and homo-logs of bradykinin, show maxima at 220 nm and minima at 235 nm which are independent of changes in solvent pd temperature. None of the analogs, e.g. D-Pro²-BK or D-Phe^5,8-bradykinin, having different spectra possessed biological activity. This suggests that it is unlikely that highly ordered analogs of amino acid composition and sequence similar to bradykinin would possess biological activity. The conclusion that bradykinin exists as a disordered chain has recently received support from an independent molecular orbital computation of the molecular conformation of minimum energy (3).