title: Functional GPCR microarrays.
abstract: This paper describes G-protein-coupled receptor (GPCR) microarrays on porous glass substrates and functional assays based on the binding of a europium-labeled GTP analogue. The porous glass slides were made by casting a glass frit on impermeable glass slides and then coating with gamma-aminopropyl silane (GAPS). The emitted fluorescence was captured on an imager with a time-gated intensified CCD detector. Microarrays of the neurotensin receptor 1, the cholinergic receptor muscarinic 2, the opioid receptor mu, and the cannabinoid receptor 1 were fabricated by pin printing. The selective agonism of each of the receptors was observed. The screening of potential antagonists was demonstrated using a cocktail of agonists. The amount of activation observed was sufficient to permit determinations of EC50 and IC50. Such microarrays could potentially streamline drug discovery by helping integrate primary screening with selectivity and safety screening without compromising the essential functional information obtainable from cellular assays.
authors.affiliation: Science and Technology Division, Corning Inc., Corning, NY 14831, USA.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Hong
authors.forename: Brian L
authors.initials: BL
authors.lastname: Webb
authors.forename: Hui
authors.initials: H
authors.lastname: Su
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Mozdy
authors.forename: Ye
authors.initials: Y
authors.lastname: Fang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Beck
authors.forename: Ann M
authors.initials: AM
authors.lastname: Ferrie
authors.forename: Srikanth
authors.initials: S
authors.lastname: Raghavan
authors.forename: John
authors.initials: J
authors.lastname: Mauro
authors.forename: Alain
authors.initials: A
authors.lastname: Carre
authors.forename: Dirk
authors.initials: D
authors.lastname: Müeller
authors.forename: Fang
authors.initials: F
authors.lastname: Lai
authors.forename: Brian
authors.initials: B
authors.lastname: Rasnow
authors.forename: Michael
authors.initials: M
authors.lastname: Johnson
authors.forename: Hosung
authors.initials: H
authors.lastname: Min
authors.forename: John
authors.initials: J
authors.lastname: Salon
authors.forename: Joydeep
authors.initials: J
authors.lastname: Lahiri
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods; D005456:Fluorescent Dyes; D008024:Ligands; D040081:Protein Array Analysis / Q000295:instrumentation / Q000379:methods*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*
chemical_list: D005456:Fluorescent Dyes; D008024:Ligands; D043562:Receptors, G-Protein-Coupled