Subtlety of the structure-affinity and structure-efficacy relationships around a nonpeptide oxytocin receptor agonist.
Very few nonpeptide oxytocin agonists have currently been reported, and none of them seem suitable for the in vivo investigation of the oxytocin mediated functions. In an attempt to rationalize the design of better tools, we have systematically studied the structural determinants of the affinity and efficacy of representative ligands of the V(1a), V(2), and OT receptor subtypes. Despite apparently obvious similarity between the ligand structures on one hand, and between the receptor subtypes on the other hand, the binding affinity and the functional activity profiles of truncated and hybrid ligands highlight the subtlety of ligand-receptor interactions for obtaining nonpeptide OT receptor agonists.
Frantz
Marie-Céline
MC
Laboratoire d'Innovation Thérapeutique, UMR 7200 CNRS/Université de Strasbourg, Faculte de Pharmacie, 74 route du Rhin, BP60024, 67401 Illkirch, France.
Rodrigo
Jordi
J
Boudier
Laure
L
Durroux
Thierry
T
Mouillac
Bernard
B
Hibert
Marcel
M
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011869:Radioligand Assay; D018045:Receptors, Oxytocin / Q000819:agonists* / Q000037:antagonists & inhibitors; D017483:Receptors, Vasopressin / Q000819:agonists; D013329:Structure-Activity Relationship
D065092:Antidiuretic Hormone Receptor Antagonists; D008024:Ligands; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D001569:Benzodiazepines