Michael acceptor approach to the design of new salvinorin A-based high affinity ligands for the kappa-opioid receptor.
European journal of medicinal chemistry October 6, 2014 Prabhakar R Polepally, Krzysztof Huben, Eyal Vardy et al. 28 citations
Salvinorin A, a compound from the plant Salvia divinorum, binds strongly and selectively to the κ-opioid receptor (KOR). A new series of salvinorin A derivatives with reactive Michael acceptor groups at C-2 was created to explore how the compound interacts with the receptor. Most of these derivatives retained high affinity for KOR, and some also bound to the μ-opioid receptor (MOR). None showed wash-resistant irreversible binding. Using the KOR crystal structure, mutagenesis data, and other methods, the researchers identified possible ways the new compounds interact with both KOR and MOR.