Journal article

Development and Application of Subtype-Selective Fluorescent Antagonists for the Study of the Human Adenosine A(1) Receptor in Living Cells

Eleonora Comeo, Phuc Trinh, Anh T Nguyen, Cameron J Nowell, Nicholas D Kindon, Mark Soave, Leigh A Stoddart, Jonathan M White, Stephen J Hill, Barrie Kellam, Michelle L Halls, Lauren T May, Peter J Scammells

JOURNAL OF MEDICINAL CHEMISTRY | AMER CHEMICAL SOC | Published : 2021

Abstract

The adenosine A1 receptor (A1AR) is a G-protein-coupled receptor (GPCR) that provides important therapeutic opportunities for a number of conditions including congestive heart failure, tachycardia, and neuropathic pain. The development of A1AR-selective fluorescent ligands will enhance our understanding of the subcellular mechanisms underlying A1AR pharmacology facilitating the development of more efficacious and selective therapies. Herein, we report the design, synthesis, and application of a novel series of A1AR-selective fluorescent probes based on 8-functionalized bicyclo[2.2.2]octylxanthine and 3-functionalized 8-(adamant-1-yl) xanthine scaffolds. These fluorescent conjugates allowed q..

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University of Melbourne Researchers

Grants

Awarded by Medical Research Council


Awarded by Australian Research Council (ARC Discovery Project)


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Funding Acknowledgements

The work was funded by the Medical Research Council (Grant number MR/N020081/1 to B.K. and S.J.H.), the Australian Research Council (ARC Discovery Project Grant DP19010145 to P.J.S.), the National Health and Medical Research Council of Australia (NHMRC) (Grant number APP1145420 to L.T.M. and S.J.H.; and APP1147291 to L.T.M.), the Monash Fellowship (from the faculty of Pharmacy and Pharmaceutical Sciences and Monash University to M.L.H.), and the Centre of Membrane Proteins and Receptors (COMPARE). This work was supported by the Nottingham-Monash Joint Doctoral Training Centre program. We thank Dr. Jason Dang for assistance with the spectroscopy work. L.T.M. is an Australian Heart Foundation Future Leader Fellow.