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Various modifications of the amphipathic dynorphin A pharmacophore for rat brain bradykinin receptors
Author(s) -
Lee Yeon Sun,
Kupp Robert,
Remesic Michael V.,
RamosColon Cyf,
Hall Sara M.,
Chan Christopher,
Rankin David,
Lai Josephine,
Porreca Frank,
Hruby Victor J.
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12789
Subject(s) - pharmacophore , dynorphin , bradykinin , chemistry , receptor , dynorphin a , opioid peptide , pharmacology , biochemistry , opioid , stereochemistry , biology
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.