Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors

As a unique endogenous opioid ligand, dynorphin A shows paradoxical neuroexcitatory effects at bradykinin receptors, and the effects are known to be amplified by the upregulation of dynorphin A under chronic pain and inflammatory conditions. In our earlier structure–activity relationship studies, the amphipathic dynorphin A fragment, [ D es‐ A rg 7 ]‐ D yn A ‐(4–11), was identified as a pharmacophore for the bradykinin receptors along with key structural features. Here, further modifications of the pharmacophore showed that the position of a P ro residue is also an important feature because of its role in making (or disrupting) a β‐turn or 3 10 helix structure which is crucial for receptor recognition.