Research Repository

See what's under the surface


Visualising ligand-binding to a GPCR in vivo using nanoBRET (2018)
Journal Article
Carvalheira Alcobia, D., Ziegler, A. I., Kondrashov, A., Comeo, E., Mistry, S., Kellam, B., …Sloan, E. K. (2018). Visualising ligand-binding to a GPCR in vivo using nanoBRET. iScience, 6(8), (280-288). doi:10.1016/j.isci.2018.08.006. ISSN 2589-0042

The therapeutic action of a drug depends on its ability to engage with its molecular target in vivo. However, current drug discovery strategies quantify drug levels within organs rather than determine the binding of drugs directly to their specific m... Read More

Molecular pharmacology of VEGF-A isoforms: binding and signalling at VEGFR2 (2018)
Journal Article
Peach, C., Mignone, V., Arruda, M., Alcobia, D., Hill, S., Kilpatrick, L., & Woolard, J. (2018). Molecular pharmacology of VEGF-A isoforms: binding and signalling at VEGFR2. International Journal of Molecular Sciences, 19(4), doi:10.3390/ijms19041264. ISSN 1661-6596

Vascular endothelial growth factor-A (VEGF-A) is a key mediator of angiogenesis, signalling via the class IV tyrosine kinase receptor family of VEGF Receptors (VEGFRs). Although VEGF-A ligands bind to both VEGFR1 and VEGFR2, they primarily signal via... Read More

Synthesis and evaluation of the first fluorescent antagonists of the human P2Y2 receptor based on AR-C118925 (2018)
Journal Article
Conroy, S., Kindon, N., Glenn, J., Stoddart, L. A., Lewis, R. J., Hill, S. J., …Stocks, M. J. (2018). Synthesis and evaluation of the first fluorescent antagonists of the human P2Y2 receptor based on AR-C118925. Journal of Medicinal Chemistry, 61(7), doi:10.1021/acs.jmedchem.8b00139. ISSN 0022-2623

The human P2Y2 receptor (hP2Y2R) is a G protein-coupled receptor that shows promise as a therapeutic target for many important conditions including anti-metastatic cancer therapy and more recently for the treatment of idiopathic pulmonary fibrosis. A... Read More

Development of novel fluorescent histamine H₁-receptor antagonists to study ligand-binding kinetics in living cells (2018)
Journal Article
antagonists to study ligand-binding kinetics in living cells. Scientific Reports, 8, doi:10.1038/s41598-018-19714-2. ISSN 2045-2322

The histamine H1-receptor (H1R) is an important mediator of allergy and inflammation. H1R antagonists have particular clinical utility in allergic rhinitis and urticaria. Here we have developed six novel fluorescent probes for this receptor that are... Read More

Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease (2017)
Journal Article
Baker, J. G., Gardiner, S. M., Woolard, J., Fromont, C., Jadhav, G. P., Mistry, S. N., …Fischer, P. M. (2017). Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease. FASEB Journal, 31(7), doi:10.1096/fj.201601305R. ISSN 0892-6638

β-Blockers reduce mortality and improve symptoms in people with heart disease. However, current clinically available β-blockers have poor selectivity for the cardiac β1-adrenoceptor (AR) over the lung β2-AR. Unwanted β2-blockade risks causing life-th... Read More

The use of fluorescence correlation spectroscopy to characterize the molecular mobility of fluorescently labelled G protein-coupled receptors (2016)
Journal Article
Kilpatrick, L. E., & Hill, S. J. (in press). The use of fluorescence correlation spectroscopy to characterize the molecular mobility of fluorescently labelled G protein-coupled receptors. Biochemical Society Transactions, 44(2), doi:10.1042/BST20150285. ISSN 0300-5127

The membranes of living cells have been shown to be highly organized into distinct microdomains, which has spatial and temporal consequences for the interaction of membrane bound receptors and their signalling partners as complexes. Fluorescence corr... Read More

Fragment-based discovery of subtype-selective adenosine receptor ligands from homology models (2015)
Journal Article
Ranganathan, A., Stoddart, L. A., Hill, S. J., & Carlsson, J. (2015). Fragment-based discovery of subtype-selective adenosine receptor ligands from homology models. Journal of Medicinal Chemistry, 58(24), doi:10.1021/acs.jmedchem.5b01120. ISSN 0022-2623

Fragment-based lead discovery (FBLD) holds great promise for drug discovery, but applications to G protein-coupled receptors (GPCRs) have been limited by a lack of sensitive screening techniques and scarce structural information. If virtual screening... Read More

An automated quasi-continuous capillary refill timing device (2015)
Journal Article
Blaxter, L., Morris, D. E., Crowe, J. A., Henry, C., Hill, S. J., Sharkey, D., …Hayes-Gill, B. R. (in press). An automated quasi-continuous capillary refill timing device. Physiological Measurement, 37(1), doi:10.1088/0967-3334/37/1/83. ISSN 0967-3334

Capillary refill time (CRT) is a simple means of cardiovascular assessment which is widely used in clinical care. Currently, CRT is measured through manual assessment of the time taken for skin tone to return to normal colour following blanching of t... Read More

Application of BRET to monitor ligand binding to GPCRs (2015)
Journal Article
Stoddart, L. A., Johnstone, E. K., Wheal, A. J., Goulding, J., Robers, M. B., Machleidt, T., …Pfleger, K. D. (in press). Application of BRET to monitor ligand binding to GPCRs. Nature Methods, 12, doi:10.1038/nmeth.3398. ISSN 1548-7091

Bioluminescence resonance energy transfer (BRET) is a well-established method for investigating protein-protein interactions. Here we present a BRET approach to monitor ligand binding to G protein–coupled receptors (GPCRs) on the surface of living ce... Read More