All Outputs (21)

Role of G protein‐coupled receptor kinases (GRKs) in β2‐adrenoceptor‐mediated glucose uptake (2024)
Journal Article
Ham, S., Mukaida, S., Sato, M., Keov, P., Bengtsson, T., Furness, S., …Hutchinson, D. S. (2024). Role of G protein‐coupled receptor kinases (GRKs) in β2‐adrenoceptor‐mediated glucose uptake. Pharmacology Research and Perspectives, 12(1), Article e1176. https://doi.org/10.1002/prp2.1176

Truncation of the C‐terminal tail of the β2‐AR, transfection of βARKct or over‐expression of a kinase‐dead GRK mutant reduces isoprenaline‐stimulated glucose uptake, indicating that GRK is important for this response. We explored whether phosphorylat... Read More about Role of G protein‐coupled receptor kinases (GRKs) in β2‐adrenoceptor‐mediated glucose uptake.

ThermoBRET: A Ligand-Engagement Nanoscale Thermostability Assay Applied to GPCRs** (2023)
Journal Article
Hoare, B. L., Tippett, D. N., Kaur, A., Cullum, S. A., Miljuš, T., Koers, E. J., …Veprintsev, D. B. (2024). ThermoBRET: A Ligand-Engagement Nanoscale Thermostability Assay Applied to GPCRs**. ChemBioChem, 25(2), Article e202300459. https://doi.org/10.1002/cbic.202300459

Measurements of membrane protein thermostability reflect ligand binding. Current thermostability assays often require protein purification or rely on pre-existing radiolabelled or fluorescent ligands, limiting their application to established targets... Read More about ThermoBRET: A Ligand-Engagement Nanoscale Thermostability Assay Applied to GPCRs**.

A time-resolved Förster resonance energy transfer assay to investigate inhibitor binding to ABCG2 (2023)
Working Paper
Mitchell-White, J. I., Briggs, D. A., Mistry, S. J., Mbiwan, H. A., Kellam, B., Holliday, N. D., …Kerr, I. D. A time-resolved Förster resonance energy transfer assay to investigate inhibitor binding to ABCG2

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 p... Read More about A time-resolved Förster resonance energy transfer assay to investigate inhibitor binding to ABCG2.

Design, Synthesis, and Application of Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the CXC Chemokine Receptor 2 (2023)
Journal Article
Casella, B. M., Farmer, J. P., Nesheva, D. N., Williams, H. E., Charlton, S. J., Holliday, N. D., …Mistry, S. N. (2023). Design, Synthesis, and Application of Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the CXC Chemokine Receptor 2. Journal of Medicinal Chemistry, https://doi.org/10.1021/acs.jmedchem.3c00849

The inhibition of CXC chemokine receptor 2 (CXCR2), a key inflammatory mediator, is a potential strategy in the treatment of several pulmonary diseases and cancers. The complexity of endogenous chemokine interaction with the orthosteric binding site... Read More about Design, Synthesis, and Application of Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the CXC Chemokine Receptor 2.

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.

Development of fluorescent peptide G protein-coupled receptor activation biosensors for NanoBRET characterization of intracellular allosteric modulators (2022)
Journal Article
Farmer, J. P., Mistry, S. N., Laughton, C. A., & Holliday, N. D. (2022). Development of fluorescent peptide G protein-coupled receptor activation biosensors for NanoBRET characterization of intracellular allosteric modulators. FASEB Journal, 36(11), Article e22576. https://doi.org/10.1096/fj.202201024R

G protein-coupled receptors (GPCRs) are widely therapeutically targeted, and recent advances in allosteric modulator development at these receptors offer further potential for exploitation. Intracellular allosteric modulators (IAM) represent a class... Read More about Development of fluorescent peptide G protein-coupled receptor activation biosensors for NanoBRET characterization of intracellular allosteric modulators.

Optical control of the β2-adrenergic receptor with opto-prop-2: A cis-active azobenzene analog of propranolol (2022)
Journal Article
Bosma, R., Dijon, N. C., Zheng, Y., Schihada, H., Hauwert, N. J., Shi, S., …Leurs, R. (2022). Optical control of the β2-adrenergic receptor with opto-prop-2: A cis-active azobenzene analog of propranolol. iScience, 25(9), Article 104882. https://doi.org/10.1016/j.isci.2022.104882

In this study, we synthesized and evaluated new photoswitchable ligands for the beta-adrenergic receptors β1-AR and β2-AR, applying an azologization strategy to the first-generation beta-blocker propranolol. The resulting compounds (Opto-prop-1, -2,... Read More about Optical control of the β2-adrenergic receptor with opto-prop-2: A cis-active azobenzene analog of propranolol.

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.

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.

Red-Emitting Dibenzodiazepinone Derivatives as Fluorescent Dualsteric Probes for the Muscarinic Acetylcholine M2 Receptor (2020)
Journal Article
She, X., Pegoli, A., Gruber, C. G., Wifling, D., Carpenter, J., Hübner, H., …Keller, M. (2020). Red-Emitting Dibenzodiazepinone Derivatives as Fluorescent Dualsteric Probes for the Muscarinic Acetylcholine M2 Receptor. Journal of Medicinal Chemistry, 63(8), 4133-4154. https://doi.org/10.1021/acs.jmedchem.9b02172

Fluorescently labeled dibenzodiazepinone-type muscarinic acetylcholine receptor (MR) antagonists, including dimeric ligands, were prepared using red-emitting cyanine dyes. Probes containing a fluorophore with negative charge showed high M2R affinitie... Read More about Red-Emitting Dibenzodiazepinone Derivatives as Fluorescent Dualsteric Probes for the Muscarinic Acetylcholine M2 Receptor.

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.

Fluorescence Labeling of Neurotensin(8–13) via Arginine Residues Gives Molecular Tools with High Receptor Affinity (2019)
Journal Article
Bernhardt, G., Keller, M., Mahuroof, S. A., Hong Yee, V., Carpenter, J., Schindler, L., …Holliday, N. D. (2020). Fluorescence Labeling of Neurotensin(8–13) via Arginine Residues Gives Molecular Tools with High Receptor Affinity. ACS Medicinal Chemistry Letters, 11, 16-22. https://doi.org/10.1021/acsmedchemlett.9b00462

Fluorescence-labeled receptor ligands have emerged as valuable molecular tools, being indispensable for studying receptor–ligand interactions by fluorescence-based techniques such as high-content imaging, fluorescence microscopy, and fluorescence pol... Read More about Fluorescence Labeling of Neurotensin(8–13) via Arginine Residues Gives Molecular Tools with High Receptor Affinity.

The peptide PnPP-19, a spider toxin derivative, activates ?-opioid receptors and modulates calcium channels (2018)
Journal Article
Freitas, A. C., Peigneur, S., Macedo, F. H., Menezes-Filho, J. E., Millns, P., Medeiros, L. F., …de Lima, M. E. (2018). The peptide PnPP-19, a spider toxin derivative, activates μ-opioid receptors and modulates calcium channels. Toxins, 10(1), 1-12. https://doi.org/10.3390/toxins10010043

The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it represents part of the primary structure of the toxin ?-CNTX-Pn1c (PnTx2-6), isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests suggest that PnPP-19... Read More about The peptide PnPP-19, a spider toxin derivative, activates ?-opioid receptors and modulates calcium channels.

Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors (2017)
Journal Article
Sykes, D. A., Moore, H., Stott, L., Holliday, N., Javitch, J. A., Lane, J. R., & Charlton, S. J. (2017). Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors. Nature Communications, 8(1), Article 763. https://doi.org/10.1038/s41467-017-00716-z

Atypical antipsychotic drugs (APDs) have been hypothesized to show reduced extrapyramidal side effects (EPS) due to their rapid dissociation from the dopamine D2 receptor. However, support for this hypothesis is limited to a relatively small number o... Read More about Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors.

Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15 (2016)
Journal Article
Liu, M., Richardson, R. R., Mountford, S. J., Zhang, L., Tempone, M. H., Herzog, H., …Thompson, P. E. (2016). Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15. Bioconjugate Chemistry, 27(9), 2166-2175. https://doi.org/10.1021/acs.bioconjchem.6b00376

Traceable truncated Neuropeptide Y (NPY) analogues with Y₁ receptor (Y₁R) affinity and selectivity are highly desirable tools in studying receptor location, regulation, and biological functions. A range of fluorescently labeled analogues of a reporte... Read More about Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15.

Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach (2016)
Journal Article
Liu, M., Mountford, S. J., Richardson, R. R., Groenen, M., Holliday, N. D., & Thompson, P. E. (2016). Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach. Journal of Medicinal Chemistry, 59(13), 6059-6069. https://doi.org/10.1021/acs.jmedchem.6b00310

The dimeric peptide 1 (BVD-74D, as a diastereomeric mixture) is a potent and selective Neuropeptide Y Y4 receptor agonist. It represents a valuable candidate in developing traceable ligands for pharmacological studies of Y4 receptors, and as a lead c... Read More about Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach.

Plasma membrane dynamics and tetrameric organisation of ABCG2 transporters in mammalian cells revealed by single particle imaging techniques (2015)
Journal Article
Wong, K., Briddon, S. J., Holliday, N. D., & Kerr, I. D. (2016). Plasma membrane dynamics and tetrameric organisation of ABCG2 transporters in mammalian cells revealed by single particle imaging techniques. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1863(1), 19-29. https://doi.org/10.1016/j.bbamcr.2015.10.002

ABCG2 is one of three human ATP binding cassette (ABC) transporters involved in the export from cells of a chemically and structurally diverse range of compounds. This multidrug efflux capability, together with a broad tissue distribution in the body... Read More about Plasma membrane dynamics and tetrameric organisation of ABCG2 transporters in mammalian cells revealed by single particle imaging techniques.

Biased Gs versus Gq proteins and ?-arrestin signaling in the NK1 receptor determined by interactions in the water hydrogen bond network (2015)
Journal Article
Valentin-Hansen, L., Frimurer, T. M., Mokrosinski, J., Holliday, N. D., & Schwartz, T. W. (2015). Biased Gs versus Gq proteins and ?-arrestin signaling in the NK1 receptor determined by interactions in the water hydrogen bond network. Journal of Biological Chemistry, 290(40), 24495-24508. https://doi.org/10.1074/jbc.m115.641944

X-ray structures, molecular dynamics simulations, and mutational analysis have previously indicated that an extended water hydrogen bond network between trans-membranes I-III, VI, and VII constitutes an allosteric interface essential for stabilizing... Read More about Biased Gs versus Gq proteins and ?-arrestin signaling in the NK1 receptor determined by interactions in the water hydrogen bond network.

A G protein-coupled receptor dimer imaging assay reveals selectively modified pharmacology of neuropeptide Y Y1/Y5 receptor heterodimers (2015)
Journal Article
Kilpatrick, L. E., Humphrys, L. J., & Holliday, N. D. (in press). A G protein-coupled receptor dimer imaging assay reveals selectively modified pharmacology of neuropeptide Y Y1/Y5 receptor heterodimers. Molecular Pharmacology, 87(4), https://doi.org/10.1124/mol.114.095356

The ability of G protein-coupled receptors (GPCRs) to form dimers, and particularly heterodimers, offers potential for targeted therapeutics with improved selectivity. However, studying dimer pharmacology is challenging, because of signaling cross-ta... Read More about A G protein-coupled receptor dimer imaging assay reveals selectively modified pharmacology of neuropeptide Y Y1/Y5 receptor heterodimers.