All Outputs (58)

Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor (2014)
Journal Article

Benzylquinolone carboxylic acid (BQCA) is an unprecedented example of a selective positive allosteric modulator of acetylcholine at the M1 muscarinic acetylcholine receptor (mAChR). To probe the structural basis underlying its selectivity, we utilize... Read More about Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor.

A structure-activity analysis of biased agonism at the dopamine D2 receptor. (2013)
Journal Article

Biased agonism offers an opportunity for the medicinal chemist to discover pathway-selective ligands for GPCRs. A number of studies have suggested that biased agonism at the dopamine D2 receptor (D2R) may be advantageous for the treatment of neuropsy... Read More about A structure-activity analysis of biased agonism at the dopamine D2 receptor..

Reverse Engineering of the Selective Agonist TBPB Unveils Both Orthosteric and Allosteric Modes of Action at the M1 Muscarinic Acetylcholine Receptor (2013)
Journal Article

Recent interest in the M1 muscarinic acetylcholine (ACh) receptor (mAChR) has led to the discovery of various selective agonists for the receptor. The novel selective agonist 1-(1′-(2-methylbenzyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-1 (... Read More about Reverse Engineering of the Selective Agonist TBPB Unveils Both Orthosteric and Allosteric Modes of Action at the M1 Muscarinic Acetylcholine Receptor.

Allosteric approaches to GPCR drug discovery (2013)
Journal Article

Synthesis, functional and binding profile of (R)-apomorphine based homobivalent ligands targeting the dopamine D2 receptor (2013)
Journal Article

Bivalent ligands represent useful tools to investigate the phenomenon of GPCR dimerization. We synthesized bivalent ligands based on (R)-apomorphine with variations in spacer length, and assessed these compounds in functional and binding assays at th... Read More about Synthesis, functional and binding profile of (R)-apomorphine based homobivalent ligands targeting the dopamine D2 receptor.

Bridging the gap: bitopic ligands of G-protein-coupled receptors (2012)
Journal Article

Although classical approaches to G-protein-coupled receptor (GPCR) drug design have targeted the orthosteric binding site, potentially all GPCRs possess druggable allosteric sites. In addition, it is clear that GPCRs can adopt multiple active states... Read More about Bridging the gap: bitopic ligands of G-protein-coupled receptors.

Structure-activity relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A) (2010)
Journal Article

Nicotinic acid (niacin) has been used for decades as an antidyslipidemic drug in man. Its main target is the hydroxy-carboxylic acid receptor HCA2 (GPR109A), a G protein-coupled receptor. Other acids and esters such as methyl fumarate also interact w... Read More about Structure-activity relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A).

Characterization of [3H]LUF5834: A novel non-ribose high-affinity agonist radioligand for the adenosine A1 receptor (2010)
Journal Article

The adenosine A(1) receptor is a promising therapeutic target for neurological disorders such as cognition deficits and is involved in cardiovascular preconditioning. Classically adenosine receptor agonists were all derivatives of adenosine, and thou... Read More about Characterization of [3H]LUF5834: A novel non-ribose high-affinity agonist radioligand for the adenosine A1 receptor.

Hybrid ortho/allosteric ligands for the adenosine A(1) receptor (2010)
Journal Article

Many G protein-coupled receptors (GPCRs), including the adenosine A(1) receptor (A(1)AR), have been shown to be allosterically modulated by small molecule ligands. So far, in the absence of structural information, the exact location of the allosteric... Read More about Hybrid ortho/allosteric ligands for the adenosine A(1) receptor.

Structure-Based Discovery of Novel Chemotypes for Adenosine A2A Receptor Antagonists (2010)
Journal Article

The recent progress in crystallography of G-protein coupled receptors opens an unprecedented venue for structure-based GPCR drug discovery. To test efficiency of the structure-based approach, we performed molecular docking and virtual ligand screenin... Read More about Structure-Based Discovery of Novel Chemotypes for Adenosine A2A Receptor Antagonists.

Ligand binding and subtype selectivity of the human A(2A) adenosine receptor: identification and characterization of essential amino acid residues (2010)
Journal Article

The crystal structure of the human A(2A) adenosine receptor bound to the A(2A) receptor-specific antagonist, ZM241385, was recently determined at 2.6-A resolution. Surprisingly, the antagonist binds in an extended conformation, perpendicular to the p... Read More about Ligand binding and subtype selectivity of the human A(2A) adenosine receptor: identification and characterization of essential amino acid residues.

A novel chemogenomics analysis of G protein-coupled receptors (GPCRs) and their ligands: a potential strategy for receptor de-orphanization (2010)
Journal Article

BACKGROUND:G protein-coupled receptors (GPCRs) represent a family of well-characterized drug targets with significant therapeutic value. Phylogenetic classifications may help to understand the characteristics of individual GPCRs and their subtypes. P... Read More about A novel chemogenomics analysis of G protein-coupled receptors (GPCRs) and their ligands: a potential strategy for receptor de-orphanization.

The endocannabinoid 2-arachidonylglycerol is a negative allosteric modulator of the human A3 adenosine receptor (2009)
Journal Article

Studies of endogenous cannabinoid agonists, such as 2-arachidonylglycerol (2-AG), have revealed their potential to exert modulatory actions on other receptor systems in addition to their ability to activate cannabinoid receptors. This study investiga... Read More about The endocannabinoid 2-arachidonylglycerol is a negative allosteric modulator of the human A3 adenosine receptor.

The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist (2008)
Journal Article

The adenosine class of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) mediates the important role of extracellular adenosine in many physiological processes and is antagonized by caffeine. We have determined t... Read More about The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist.

G Protein Coupling and Ligand Selectivity of the D2L and D3 Dopamine Receptors (2008)
Journal Article

The human dopamine D2L receptor couples promiscuously to multiple members of the Gαi/o subfamily. Despite the high homology of the D2L and D3 receptors, the G protein coupling specificity of the human D3 receptor is less clearly characterized. The pr... Read More about G Protein Coupling and Ligand Selectivity of the D2L and D3 Dopamine Receptors.

Antibodies that identify only the active conformation of G(i) family G protein alpha subunits (2008)
Journal Article

Production of antisera able to recognize individual heterotrimeric G protein alpha subunits resulted in rapid expansion of information on their distribution and function. However, no antibodies that specifically recognize the active state have been a... Read More about Antibodies that identify only the active conformation of G(i) family G protein alpha subunits.

Novel pharmacological applications of G-protein-coupled receptor-G protein fusions (2007)
Journal Article

Single, bi-functional polypeptides consisting of a G-protein-coupled receptor (GPCR) linked directly to a G protein alpha subunit have been employed for a number of years to study many aspects of signal initiation, including the roles of post-transla... Read More about Novel pharmacological applications of G-protein-coupled receptor-G protein fusions.

Protean agonism at the dopamine D2 receptor: (S)-3-(3-hydroxyphenyl)-N-propylpiperidine is an agonist for activation of Go1 but an antagonist/inverse agonist for Gi1,Gi2, and Gi3 (2007)
Journal Article

A range of ligands displayed agonism at the long isoform of the human dopamine D(2) receptor, whether using receptor-G protein fusions or membranes of cells in which pertussis toxin-resistant mutants of individual Galpha(i)-family G proteins could be... Read More about Protean agonism at the dopamine D2 receptor: (S)-3-(3-hydroxyphenyl)-N-propylpiperidine is an agonist for activation of Go1 but an antagonist/inverse agonist for Gi1,Gi2, and Gi3.