All Outputs (29)

Real-Time Ligand Binding of Fluorescent VEGF-A Isoforms that Discriminate between VEGFR2 and NRP1 in Living Cells (2018)
Journal Article
Peach, C. J., Kilpatrick, L. E., Friedman-Ohana, R., Zimmerman, K., Robers, M. B., Wood, K. V., Woolard, J., & Hill, S. J. (2018). Real-Time Ligand Binding of Fluorescent VEGF-A Isoforms that Discriminate between VEGFR2 and NRP1 in Living Cells. Cell Chemical Biology, 25(10), 1208-1218.e5. https://doi.org/10.1016/j.chembiol.2018.06.012

© 2018 The Author(s) Fluorescent VEGF-A isoforms have been evaluated for their ability to discriminate between VEGFR2 and NRP1 in real-time ligand binding studies in live cells using BRET. To enable this, we synthesized single-site (N-terminal cystei... Read More about Real-Time Ligand Binding of Fluorescent VEGF-A Isoforms that Discriminate between VEGFR2 and NRP1 in Living Cells.

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), Article 1264. https://doi.org/10.3390/ijms19041264

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 about Molecular pharmacology of VEGF-A isoforms: binding and signalling at VEGFR2.

A monoclonal antibody raised against a thermo-stabilised β1-adrenoceptor interacts with extracellular loop 2 and acts as a negative allosteric modulator of a sub-set of 1- adrenoceptors expressed in stable cell lines (2017)
Journal Article
Soave, M., Cseke, G., Hutchings, C. J., Brown, A. J., Woolard, J., & Hill, S. J. (2018). A monoclonal antibody raised against a thermo-stabilised β1-adrenoceptor interacts with extracellular loop 2 and acts as a negative allosteric modulator of a sub-set of 1- adrenoceptors expressed in stable cell lines. Biochemical Pharmacology, 147, https://doi.org/10.1016/j.bcp.2017.10.015

Recent interest has focused on antibodies that can discriminate between different receptor conformations. Here we have characterised the effect of a monoclonal antibody (mAb3), raised against a purified thermo-stabilised turkey β1-adrenoceptor (β1AR-... Read More about A monoclonal antibody raised against a thermo-stabilised β1-adrenoceptor interacts with extracellular loop 2 and acts as a negative allosteric modulator of a sub-set of 1- adrenoceptors expressed in stable cell lines.

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., Thompson, K. S., Kellam, B., Hill, S. J., & Fischer, P. M. (2017). Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease. FASEB Journal, 31(7), 3150-3166. https://doi.org/10.1096/fj.201601305R

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 about Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease.

Real-time analysis of the binding of fluorescent VEGF165a to VEGFR2 in living cells: Effect of receptor tyrosine kinase inhibitors and fate of internalized agonist-receptor complexes (2017)
Journal Article
Kilpatrick, L. E., Friedman-Ohana, R., Alcobia, D. C., Riching, K., Peach, C. J., Wheal, A. J., Briddon, S. J., Robers, M. B., Zimmerman, K., Machleidt, T., Wood, K. V., Woolard, J., & Hill, S. J. (2017). Real-time analysis of the binding of fluorescent VEGF165a to VEGFR2 in living cells: Effect of receptor tyrosine kinase inhibitors and fate of internalized agonist-receptor complexes. Biochemical Pharmacology, 136, 62-75. https://doi.org/10.1016/j.bcp.2017.04.006

© 2017 The Authors Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. Here we have used a novel stoichiometric protein-labeling method to generate a fluorescent variant of VEGF (VEGF165a-TMR) labeled on a single cyste... Read More about Real-time analysis of the binding of fluorescent VEGF165a to VEGFR2 in living cells: Effect of receptor tyrosine kinase inhibitors and fate of internalized agonist-receptor complexes.

Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats (2016)
Journal Article
Carter, J. J., Fretwell, L., & Woolard, J. (2017). Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats. FASEB Journal, 31(3), 1193-1203. https://doi.org/10.1096/fj.201600749r

VEGF inhibitors, including receptor tyrosine kinase inhibitors, are used as adjunct therapies in a number of cancer treatments. An emerging issue with these drugs is that most cause hypertension. To gain insight into the physiological mechanisms invo... Read More about Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats.

Use of a new proximity assay (NanoBRET) to investigate the ligand-binding characteristics of three fluorescent ligands to the humanβ1-adrenoceptor expressed in HEK-293 cells (2016)
Journal Article
Soave, M., Stoddart, L. A., Brown, A., Woolard, J., & Hill, S. J. (2016). Use of a new proximity assay (NanoBRET) to investigate the ligand-binding characteristics of three fluorescent ligands to the humanβ1-adrenoceptor expressed in HEK-293 cells. Pharmacology Research and Perspectives, 4(5), Article e00250. https://doi.org/10.1002/prp2.250

Previous research has indicated that allosteric interactions across the dimer interface of β1-adrenoceptors may be responsible for a secondary low affinity binding conformation. Here we have investigated the potential for probe dependence, in the det... Read More about Use of a new proximity assay (NanoBRET) to investigate the ligand-binding characteristics of three fluorescent ligands to the humanβ1-adrenoceptor expressed in HEK-293 cells.

Effects of receptor tyrosine kinase inhibitors on VEGF165a- and VEGF165b-stimulated gene transcription in HEK-293 cells expressing human VEGFR2 (2015)
Journal Article
Carter, J. J., Wheal, A. J., Hill, S. J., & Woolard, J. (2015). Effects of receptor tyrosine kinase inhibitors on VEGF165a- and VEGF165b-stimulated gene transcription in HEK-293 cells expressing human VEGFR2. British Journal of Pharmacology, 172(12), https://doi.org/10.1111/bph.13116

BACKGROUND AND PURPOSE:
Receptor tyrosine kinase inhibitors (RTKIs) targeted at VEGF receptor 2 (VEGFR2) have proved to be attractive approaches to cancer therapy based on their ability to reduce angiogenesis. Here we have undertaken a quantitative... Read More about Effects of receptor tyrosine kinase inhibitors on VEGF165a- and VEGF165b-stimulated gene transcription in HEK-293 cells expressing human VEGFR2.

Monoclonal anti-β1-adrenergic receptor antibodies activate G protein signaling in the absence of β-arrestin recruitment (2013)
Journal Article
Hutchings, C. J., Cseke, G., Osborne, G., Woolard, J., Zhukov, A., Koglin, M., Jazayeri, A., Pandya-Pathak, J., Langmead, C. J., Hill, S. J., Weir, M., & Marshall, F. H. (2014). Monoclonal anti-β1-adrenergic receptor antibodies activate G protein signaling in the absence of β-arrestin recruitment. mAbs, 6(1), 246-261. https://doi.org/10.4161/mabs.27226

Thermostabilized G protein-coupled receptors used as antigens for in vivo immunization have resulted in the generation of functional agonistic anti-β1-adrenergic (β1AR) receptor monoclonal antibodies (mAbs). The focus of this study was to examine the... Read More about Monoclonal anti-β1-adrenergic receptor antibodies activate G protein signaling in the absence of β-arrestin recruitment.