Design, synthesis, and in vitro pharmacology of new radiolabeled gamma-hydroxybutyric acid analogues including photolabile analogues with irreversible binding to the high-affinity gamma-hydroxybutyric acid binding sites.
Gamma-hydroxybutyric acid (GHB) is a psychotropic compound endogenous to the brain. Despite its potential physiological significance, the complete molecular mechanisms of action remain unexplained. To facilitate the isolation and identification of the high-affinity GHB binding site, we herein report the design and synthesis of the first (125)I-labeled radioligands in the field, one of which contains a photoaffinity label which enables it to bind irreversibly to the high-affinity GHB binding sites.
Sabbatini
Paola
P
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, 2 Universitetsparken, Dk-2100 Copenhagen, Denmark.
Wellendorph
Petrine
P
Høg
Signe
S
Pedersen
Martin H F
MH
Bräuner-Osborne
Hans
H
Martiny
Lars
L
Frølund
Bente
B
Clausen
Rasmus P
RP
D000818:Animals; D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D015195:Drug Design; D006885:Hydroxybutyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008024:Ligands; D008027:Light; D019920:Photoaffinity Labels / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001386:Azides; D006885:Hydroxybutyrates; D007457:Iodine Radioisotopes; D008024:Ligands; D019920:Photoaffinity Labels; C111420:4-hydroxybutyric acid