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Philip D Mosier

6 papers in the library · 256 citations · publishing 2005-2014

Papers

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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

The neoclerodane diterpenoid salvinorin A is a major secondary metabolite isolated from the psychoactive plant Salvia divinorum. Salvinorin A has been shown to have high affinity and selectivity for the κ-opioid receptor (KOR). To study the ligand-receptor interactions that occur between salvinorin A and the KOR, a new series of salvinorin A derivatives bearing potentially reactive Michael...

Chemotype-selective modes of action of κ-opioid receptor agonists.

The Journal of biological chemistry November 29, 2013 Eyal Vardy, Philip D Mosier, Kevin J Frankowski et al.

The crystal structures of opioid receptors provide a novel platform for inquiry into opioid receptor function. The molecular determinants for activation of the κ-opioid receptor (KOR) were studied using a combination of agonist docking, functional assays, and site-directed mutagenesis. Eighteen positions in the putative agonist binding site of KOR were selected and evaluated for their effects...

CoMFA analyses of C-2 position salvinorin A analogs at the kappa-opioid receptor provides insights into epimer selectivity.

Journal of molecular graphics & modelling April 1, 2010 Donna L Mcgovern, Philip D Mosier, Bryan L. Roth et al. 16 citations

The highly potent and kappa-opioid (KOP) receptor-selective hallucinogen Salvinorin A and selected analogs have been analyzed using the 3D quantitative structure-affinity relationship technique Comparative Molecular Field Analysis (CoMFA) in an effort to derive a statistically significant and predictive model of salvinorin affinity at the KOP receptor and to provide additional statistical...

Structure-based design, synthesis, and biochemical and pharmacological characterization of novel salvinorin A analogues as active state probes of the kappa-opioid receptor.

Biochemistry July 28, 2009 Feng Yan, Ruslan V Bikbulatov, Viorel Mocanu et al. 81 citations

Salvinorin A, the most potent naturally occurring hallucinogen, has attracted an increasing amount of attention since the kappa-opioid receptor (KOR) was identified as its principal molecular target by us [Roth, B. L., et al. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 11934-11939]. Here we report the design, synthesis, and biochemical characterization of novel, irreversible, salvinorin A-derived...

Differential helical orientations among related G protein-coupled receptors provide a novel mechanism for selectivity. Studies with salvinorin A and the kappa-opioid receptor.

The Journal of biological chemistry February 2, 2007 Timothy A Vortherms, Philip D Mosier, Richard B Westkaemper et al. 40 citations

Salvinorin A, the active component of the hallucinogenic sage Salvia divinorum, is an apparently selective and highly potent kappa-opioid receptor (KOR) agonist. Salvinorin A is unique among ligands for peptidergic G protein-coupled receptors in being nonnitrogenous and lipid-like in character. To examine the molecular basis for the subtype-selective binding of salvinorin A, we utilized an...

Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors.

Biochemistry June 21, 2005 Feng Yan, Philip D Mosier, Richard B Westkaemper et al. 91 citations

Salvinorin A is a naturally occurring hallucinogenic diterpenoid from the plant Salvia divinorumthat selectively and potently activates kappa-opioid receptors (KORs). Salvinorin A is unique in that it is the only known lipid-like molecule that selectively and potently activates a G-protein coupled receptor (GPCR), which has as its endogenous agonist a peptide; salvinorin A is also the only...