Hydroxyproline Analogs of Bradykinin: Biological Activities and Solution Structures

  • John Morrow Stewart
  • A. H. Brady
  • James W. Ryan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 21)


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-Phe5,8-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).


Circular Dichroism Solid Phase Synthesis Solid Phase Peptide Synthesis Hydroxy Amino Relative Inactivity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A. H. Brady, J. M. Stewart and J. W. Ryan, in “Bradykinin and Related Kinins”, F. Sicuteri, M. Rocha e Silva and N. Back, eds., Plenum Press, New York, 1970, p. 47.Google Scholar
  2. 2.
    A. H. Brady, J. W. Ryan and J. M. Stewart, Biochem. J., 121, 179 (1971).PubMedGoogle Scholar
  3. 3.
    L. B. Kier and J. M. George, in “Molecular Orbital Studies in Chemical Pharmacology”, L. B. Kier, ed., Springer-Verlag, New York, 1970, p. 82.Google Scholar
  4. 4.
    J. M. Stewart, T. Mizoguchi and D. W. Woolley, Abstracts of American Chemical Society 153rd Meeting, Miami, Fla., March 1967, Abstract 0–206.Google Scholar
  5. 5.
    J. M. Stewart, in “Structure-Activity Relationships of Protein and Polypeptide Hormones”, M. Margoulies and F. C. Greenwood, eds., Excerpta Medica, 1971, p. 23.Google Scholar
  6. 6.
    J. M. Stewart and J. D. Young, “Solid Phase Peptide Synthesis”, W. H. Freeman, San Francisco, 1969.Google Scholar
  7. 7.
    R. B. Merrifield, J. M. Stewart and N. Jernberg, Anal. Chem., 38, 1905 (1966).PubMedCrossRefGoogle Scholar
  8. 8.
    F. W. Dunn and J. M. Stewart, J. Med. Chem., 14, 779 (1971).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1972

Authors and Affiliations

  • John Morrow Stewart
    • 1
  • A. H. Brady
    • 2
  • James W. Ryan
    • 2
  1. 1.University of Colorado School of MedicineDenverUSA
  2. 2.University of Miami School of MedicineMiamiUSA

Personalised recommendations