Design of a high affinity peptidomimetic opioid agonist from peptide pharmacophore models.
A pair of diastereomeric peptidomimetics based upon opioid receptor-binding pharmacophore models derived for a series of opioid tetrapeptides was synthesized. Both analogues display high opioid receptor affinity, moderate selectivity for the mu opioid receptor, and are potent, full agonists.
Wang
C
C
College of Pharmacy, University of Michigan, Ann Arbor 48109, USA.
McFadyen
I J
IJ
Traynor
J R
JR
Mosberg
H I
HI
D015195:Drug Design; D007700:Kinetics; D018847:Opioid Peptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D018847:Opioid Peptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu