X-ray crystal structure of the opioid ligand naltrexonazine.
The anti-anti isomer of naltrexonazine (1) was synthesized, and its configuration was confirmed by X-ray crystallography. The syn-anti isomer is readily converted to 1 under acidic conditions. The apparent equal receptor binding of 1 and syn-anti isomer indicates that isomerization of the azine moiety may take place under the conditions of biological evaluation. Two possible explanations for wash-resistant binding of 1 to opioid receptors are presented. The first possibility involves a noncovalent interaction of the ligand with the opioid receptor, and the second considers covalent binding by a receptor-based sulfhydryl group.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003460:Crystallization; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D013237:Stereoisomerism; D014961:X-Ray Diffraction
D011957:Receptors, Opioid; D009271:Naltrexone; C034637:naltrexonazine