Abstract
Psychoactive natural products have been used to study the intricate workings of various receptor systems in the central nervous system (CNS). Our studies focused on the identification of plant metabolites responsible for CNS activity and designing new ligands with high affinity to CNS receptors. Salvinorin A, the most potent naturally occurring hallucinogen isolated from the plant Salvia divinorum, has received great attention since the kappa-opiod receptor (KOR) was identified as its molecular target. Previously, extensive efforts were made to understand how salvinorin A binds to and activates KOR [1–5]. Our goal is to design a series of ligands with high affinity to KOR to further explore the ligand-receptor interactions at the molecular level. In continuation of our research work towards designing irreversible ligands [4,5], we synthesized a series of Michael acceptor type of new salvinorin A derivatives and evaluated their binding affinity to KOR, MOR and DOR.
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