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A time-resolved Förster resonance energy transfer assay to investigate drug and inhibitor binding to ABCG2 (2024)
Journal Article
Mitchell-White, J. I., Briggs, D. A., Mistry, S. J., Mbiwan, H. A., Kellam, B., Holliday, N. D., …Kerr, I. D. (2024). A time-resolved Förster resonance energy transfer assay to investigate drug and inhibitor binding to ABCG2. Archives of Biochemistry and Biophysics, 753, Article 109915. https://doi.org/10.1016/j.abb.2024.109915

The human ATP-binding cassette (ABC) transporter, ABCG2, is responsible for multidrug resistance in some tumours. Detailed knowledge of its activity is crucial for understanding drug transport and resistance in cancer, and has implications for wider... Read More about A time-resolved Förster resonance energy transfer assay to investigate drug and inhibitor binding to ABCG2.

Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3) (2023)
Journal Article
Dekkers, S., Comez, D., Karsai, N., Arimont-Segura, M., Canals, M., Caspar, B., …Stocks, M. J. (2023). Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3). ACS Medicinal Chemistry Letters, 15(1), 143–148. https://doi.org/10.1021/acsmedchemlett.3c00469

The atypical chemokine receptor 3 (ACKR3) is a receptor that induces cancer progression and metastasis in multiple cell types. Therefore, new chemical tools are required to study the role of ACKR3 in cancer and other diseases. In this study, fluoresc... Read More about Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3).

Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor (2023)
Journal Article
Dekkers, S., Caspar, B., Goulding, J., Kindon, N. D., Kilpatrick, L. E., Stoddart, L. A., …Stocks, M. J. (2023). Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor. Journal of Medicinal Chemistry, 66(7), 5208-5222. https://doi.org/10.1021/acs.jmedchem.3c00151

The C-X-C chemokine receptor type 4, or CXCR4, is a chemokine receptor found to promote cancer progression and metastasis of various cancer cell types. To investigate the pharmacology of this receptor, and to further elucidate its role in cancer, nov... Read More about Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor.

Bitter taste sensitivity in domestic dogs (Canis familiaris) and its relevance to bitter deterrents of ingestion (2022)
Journal Article
Gibbs, M., Winnig, M., Riva, I., Dunlop, N., Waller, D., Klebansky, B., …McGrane, S. J. (2022). Bitter taste sensitivity in domestic dogs (Canis familiaris) and its relevance to bitter deterrents of ingestion. PLoS ONE, 17(11), Article e0277607. https://doi.org/10.1371/journal.pone.0277607

As the most favoured animal companion of humans, dogs occupy a unique place in society. Understanding the senses of the dog can bring benefits to both the dogs themselves and their owners. In the case of bitter taste, research may provide useful info... Read More about Bitter taste sensitivity in domestic dogs (Canis familiaris) and its relevance to bitter deterrents of ingestion.

Probing the binding of interleukin-23 to individual receptor components and the IL-23 heteromeric receptor complex in living cells using NanoBRET (2021)
Journal Article
Lay, C. S., Bridges, A., Goulding, J., Briddon, S. J., Soloviev, Z., Craggs, P. D., & Hill, S. J. (2022). Probing the binding of interleukin-23 to individual receptor components and the IL-23 heteromeric receptor complex in living cells using NanoBRET. Cell Chemical Biology, 29(1), 19-29.e6. https://doi.org/10.1016/j.chembiol.2021.05.002

Interleukin-23 (IL-23) is a pro-inflammatory cytokine involved in the host defence against pathogens, but also implicated in the development of several autoimmune disorders. The IL- 23 receptor has become a key target for drug discovery but the exact... Read More about Probing the binding of interleukin-23 to individual receptor components and the IL-23 heteromeric receptor complex in living cells using NanoBRET.

Subtype selective fluorescent ligands based on ICI 118,551 to study the human β2‐adrenoceptor in CRISPR/Cas9 genome‐edited HEK293T cells at low expression levels (2021)
Journal Article
Kellam, B., White, C. W., Goulding, J., Mistry, S. J., Soave, M., Woolard, J., …Hill, S. J. (2021). Subtype selective fluorescent ligands based on ICI 118,551 to study the human β2‐adrenoceptor in CRISPR/Cas9 genome‐edited HEK293T cells at low expression levels. Pharmacology Research and Perspectives, 9(3), Article e00779. https://doi.org/10.1002/prp2.779

Fluorescent ligand technologies have proved to be powerful tools to improve our understanding of ligand-receptor interactions. Here we have characterized a small focused library of nine fluorescent ligands based on the highly selective β2-adrenocepto... Read More about Subtype selective fluorescent ligands based on ICI 118,551 to study the human β2‐adrenoceptor in CRISPR/Cas9 genome‐edited HEK293T cells at low expression levels.

Analysis of sequence divergence in mammalian abcgs predicts a structural network of residues that underlies functional divergence (2021)
Journal Article
Mitchell-White, J. I., Stockner, T., Holliday, N., Briddon, S. J., & Kerr, I. D. (2021). Analysis of sequence divergence in mammalian abcgs predicts a structural network of residues that underlies functional divergence. International Journal of Molecular Sciences, 22(6), 1-16. https://doi.org/10.3390/ijms22063012

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport... Read More about Analysis of sequence divergence in mammalian abcgs predicts a structural network of residues that underlies functional divergence.

The use of fluorescence correlation spectroscopy to monitor cell surface ?2?adrenoceptors at low expression levels in human embryonic stem cell?derived cardiomyocytes and fibroblasts (2021)
Journal Article
Goulding, J., Kondrashov, A., Mistry, S. J., Melarangi, T., Vo, N. T. N., Hoang, D. M., …Hill, S. J. (2021). The use of fluorescence correlation spectroscopy to monitor cell surface β2‐adrenoceptors at low expression levels in human embryonic stem cell‐derived cardiomyocytes and fibroblasts. FASEB Journal, 35(4), Article e21398. https://doi.org/10.1096/fj.202002268r

The importance of cell phenotype in determining the molecular mechanisms underlying ?2- adrenoceptor (?2AR) function has been noted previously when comparing responses in primary cells and recombinant model cell lines. Here, we have generated haploty... Read More about The use of fluorescence correlation spectroscopy to monitor cell surface ?2?adrenoceptors at low expression levels in human embryonic stem cell?derived cardiomyocytes and fibroblasts.

Efficient G protein coupling is not required for agonist?mediated internalization and membrane reorganization of the adenosine A 3 receptor (2021)
Journal Article
Stoddart, L. A., Kilpatrick, L. E., Corriden, R., Kellam, B., Briddon, S. J., & Hill, S. J. (2021). Efficient G protein coupling is not required for agonist?mediated internalization and membrane reorganization of the adenosine A 3 receptor. FASEB Journal, 35(4), Article e21211. https://doi.org/10.1096/fj.202001729rr

Organization of G protein-coupled receptors at the plasma membrane has been the focus of much recent attention. Advanced microscopy techniques have shown that these receptors can be localized to discrete microdomains and reorganization upon ligand ac... Read More about Efficient G protein coupling is not required for agonist?mediated internalization and membrane reorganization of the adenosine A 3 receptor.

Detection of genome-edited and endogenously expressed G protein-coupled receptors (2021)
Journal Article
Soave, M., Stoddart, L. A., White, C. W., Kilpatrick, L. E., Goulding, J., Briddon, S. J., & Hill, S. J. (2021). Detection of genome-edited and endogenously expressed G protein-coupled receptors. FEBS Journal, 288(8), 2585-2601. https://doi.org/10.1111/febs.15729

© 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. G protein-coupled receptors (GPCRs) are the largest family of membrane receptors and major targets for FDA-approved d... Read More about Detection of genome-edited and endogenously expressed G protein-coupled receptors.

A lipid-anchored neurokinin 1 receptor antagonist prolongs pain relief by a three-pronged mechanism of action targeting the receptor at the plasma membrane and in endosomes (2021)
Journal Article
Mai, Q. N., Shenoy, P., Quach, T., Retamal, J. S., Gondin, A. B., Yeatman, H. R., …Veldhuis, N. A. (2021). A lipid-anchored neurokinin 1 receptor antagonist prolongs pain relief by a three-pronged mechanism of action targeting the receptor at the plasma membrane and in endosomes. Journal of Biological Chemistry, 296, Article 100345. https://doi.org/10.1016/J.JBC.2021.100345

G-protein-coupled receptors (GPCRs) are traditionally known for signaling at the plasma membrane, but they can also signal from endosomes after internalization to control important pathophysiological processes. In spinal neurons, sustained endosomal... Read More about A lipid-anchored neurokinin 1 receptor antagonist prolongs pain relief by a three-pronged mechanism of action targeting the receptor at the plasma membrane and in endosomes.

Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells (2020)
Journal Article
Stoddart, L. A., Kindon, N. D., Otun, O., Harwood, C. R., Patera, F., Veprintsev, D. B., …Kellam, B. (2020). Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells. Communications Biology, 3(1), Article 722. https://doi.org/10.1038/s42003-020-01451-w

© 2020, The Author(s). To study the localisation of G protein-coupled receptors (GPCR) in their native cellular environment requires their visualisation through fluorescent labelling. To overcome the requirement for genetic modification of the recept... Read More about Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells.

Monitoring Allosteric Interactions with CXCR4 Using NanoBiT Conjugated Nanobodies (2020)
Journal Article
Soave, M., Heukers, R., Kellam, B., Woolard, J., Smit, M. J., Briddon, S. J., & Hill, S. J. (2020). Monitoring Allosteric Interactions with CXCR4 Using NanoBiT Conjugated Nanobodies. Cell Chemical Biology, 27, 1-12. https://doi.org/10.1016/j.chembiol.2020.06.006

© 2020 The Authors Camelid single-domain antibody fragments (nanobodies) offer the specificity of an antibody in a single 15-kDa immunoglobulin domain. Their small size allows for easy genetic manipulation of the nanobody sequence to incorporate prot... Read More about Monitoring Allosteric Interactions with CXCR4 Using NanoBiT Conjugated Nanobodies.

Heterodimeric Analogues of the Potent Y1R Antagonist 1229U91, Lacking One of the Pharmacophoric C-Terminal Structures, Retain Potent Y1R Affinity and Show Improved Selectivity over Y4R (2020)
Journal Article
Richardson, R. R., Richardson, R., Groenen, M., Liu, M., Mountford, S. J., Briddon, S. J., …Thompson, P. E. (2020). Heterodimeric Analogues of the Potent Y1R Antagonist 1229U91, Lacking One of the Pharmacophoric C-Terminal Structures, Retain Potent Y1R Affinity and Show Improved Selectivity over Y4R. Journal of Medicinal Chemistry, 63(10), 5274-5286. https://doi.org/10.1021/acs.jmedchem.0c00027

The cyclic dimeric peptide 1229U91 (GR231118) has an unusual structure and displays potent, insurmountable antagonism of the Y1 receptor. To probe the structural basis for this activity, we have prepared ring size variants and heterodimeric compounds... Read More about Heterodimeric Analogues of the Potent Y1R Antagonist 1229U91, Lacking One of the Pharmacophoric C-Terminal Structures, Retain Potent Y1R Affinity and Show Improved Selectivity over Y4R.

The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex (2020)
Journal Article
Koo, C. Z., Harrison, N., Noy, P. J., Szyroka, J., Matthews, A. L., Hsia, H. E., …Tomlinson, M. G. (2020). The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex. Journal of Biological Chemistry, 295(36), 12822-12839. https://doi.org/10.1074/jbc.RA120.012601

© 2020 Koo et al. A disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein essential for embryonic development, and its dysregulation underlies disorders such as cancer, Alzheimer's disease, and inflammation. ADAM10 is a "molecular sc... Read More about The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex.

Application of fluorescence correlation spectroscopy to study substrate binding in styrene maleic acid lipid copolymer encapsulated ABCG2 (2020)
Journal Article
Horsey, A. J., Briggs, D. A., Holliday, N. D., Briddon, S. J., & Kerr, I. D. (2020). Application of fluorescence correlation spectroscopy to study substrate binding in styrene maleic acid lipid copolymer encapsulated ABCG2. BBA - Biomembranes, 1862(6), https://doi.org/10.1016/j.bbamem.2020.183218

© 2020 The Authors ABCG2 is one of a trio of human ATP binding cassette transporters that have the ability to bind and transport a diverse array of chemical substrates out of cells. This so-called “multidrug” transport has numerous physiological cons... Read More about Application of fluorescence correlation spectroscopy to study substrate binding in styrene maleic acid lipid copolymer encapsulated ABCG2.

NanoBiT Complementation to Monitor Agonist-Induced Adenosine A1 Receptor Internalization (2019)
Journal Article
Soave, M., Kellam, B., Woolard, J., Briddon, S. J., & Hill, S. J. (2019). NanoBiT Complementation to Monitor Agonist-Induced Adenosine A1 Receptor Internalization. Slas Discovery, https://doi.org/10.1177/2472555219880475

Receptor internalization in response to prolonged agonist treatment is an important regulator of G protein–coupled receptor (GPCR) function. The adenosine A1 receptor (A1AR) is one of the adenosine receptor family of GPCRs, and evidence for its agoni... Read More about NanoBiT Complementation to Monitor Agonist-Induced Adenosine A1 Receptor Internalization.

Modulators of CXCR4 and CXCR7/ACKR3 Function (2019)
Journal Article
Adlere, I., Caspar, B., Arimont, M., Dekkers, S., Visser, K., Stuijt, J., …Leurs, R. (2019). Modulators of CXCR4 and CXCR7/ACKR3 Function. Molecular Pharmacology, 96(6), 737-752. https://doi.org/10.1124/mol.119.117663

Copyright © 2019 by The Author(s). The two G protein-coupled receptors (GPCRs) C-X-C chemokine receptor type 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are part of the class A chemokine GPCR family and represent important drug targets for hu... Read More about Modulators of CXCR4 and CXCR7/ACKR3 Function.

Probe dependency in the determination of ligand binding kinetics at a prototypical G protein-coupled receptor (2019)
Journal Article
Bosma, R., Stoddart, L. A., Georgi, V., Bouzo-Lorenzo, M., Bushby, N., Inkoom, L., …Leurs, R. (2019). Probe dependency in the determination of ligand binding kinetics at a prototypical G protein-coupled receptor. Scientific Reports, 9, Article 7906. https://doi.org/10.1038/s41598-019-44025-5

© 2019, The Author(s). Drug-target binding kinetics are suggested to be important parameters for the prediction of in vivo drug-efficacy. For G protein-coupled receptors (GPCRs), the binding kinetics of ligands are typically determined using associat... Read More about Probe dependency in the determination of ligand binding kinetics at a prototypical G protein-coupled receptor.

GRK mediates ?-opioid receptor plasma membrane reorganization (2019)
Journal Article
Gondin, A. B., Halls, M. L., Canals, M., & Briddon, S. J. (2019). GRK mediates ?-opioid receptor plasma membrane reorganization. Frontiers in Molecular Neuroscience, 12, https://doi.org/10.3389/fnmol.2019.00104

Differential regulation of the ?-opioid receptor (MOP) has been linked to the development of opioid tolerance and dependence which both limit the clinical use of opioid analgesics. At a cellular level, MOP regulation occurs via receptor phosphorylati... Read More about GRK mediates ?-opioid receptor plasma membrane reorganization.