Bradykinin, structure-activity relationships

In the late 1980s when we began the pursuit of bradykinin receptor antagonists, information of relevance to medicinal chemists was scarce. For example, not one nonpeptide antagonist of this receptor was known, nor were any series upon which to base a structure-activity relationship. Moreover, all publications described bradykinin as being highly flexible in an aqueous environment, such that no structural mimetics could be rationalized. Of course the receptors had not been cloned at that time so nothing was known about the primary sequence of the receptor or the three-dimensional structure. 

Hellberg, S., Sjostrom. M. and Wold. S. The Prediction of Bradykinin Potentiating Potency of Pentapeptides. An Example of a Peptide Quantitative Structure-Activity Relationship. Acta Chem. Scand. 1986, B40, 135-140. 

Reissmann, S., Pineda, R, Vietinghoff, G., Werner, H., Gera, L., Stewart, J.M., and Paegelow, L Structure activity relationships for bradykinin antagonists on the inhibition of cytokine release and the release of histamine. Peptides 2000, 21 527-533. 

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