ORCID Profile
0000-0003-0030-9908
Current Organisation
University of Nottingham
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Publisher: American Chemical Society (ACS)
Date: 30-12-2019
DOI: 10.1021/ACS.JMEDCHEM.9B01856
Abstract: Among class A G protein-coupled receptors (GPCR), the human adenosine A
Publisher: American Association for the Advancement of Science (AAAS)
Date: 31-03-2020
DOI: 10.1126/SCISIGNAL.AAZ3140
Abstract: Low intrinsic efficacy can explain the reduced side effects of apparently biased μ-opioid receptor agonists.
Publisher: American Chemical Society (ACS)
Date: 03-10-2019
DOI: 10.1021/ACS.JMEDCHEM.9B00864
Abstract: Haloperidol is a typical antipsychotic drug (APD) associated with an increased risk of extrapyramidal side effects (EPSs) and hyperprolactinemia relative to atypical APDs such as clozapine. Both drugs are dopamine D
Publisher: Wiley
Date: 05-2021
DOI: 10.1002/PRP2.779
Abstract: 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 β 2 ‐adrenoceptor (β 2 AR) antagonist ICI 118,551. The majority of fluorescent ICI 118,551 analogs had good affinity for the β 2 AR (pK D .0) with good selectivity over the β 1 AR (pK D .0). The most potent and selective ligands being 8c (ICI 118,551‐Gly‐Ala‐BODIPY‐FL‐X β 2 AR pK D 7.48), 9c (ICI 118,551‐βAla‐βAla‐BODIPY‐FL‐X β 2 AR pK D 7.48), 12a (ICI 118,551‐PEG‐BODIPY‐X‐630/650 β 2 AR pK D 7.56), and 12b (ICI 118,551‐PEG‐BODIPY‐FL β 2 AR pK D 7.42). 9a (ICI 118,551‐βAla‐βAla‐BODIPY‐X‐630/650) had the highest affinity at recombinant β 2 ARs (pK D 7.57), but also exhibited significant binding affinity to the β 1 AR (pK D 6.69). Nevertheless, among the red fluorescent ligands, 9a had the best imaging characteristics in recombinant HEK293 T cells and labeling was mostly confined to the cell surface. In contrast, 12a showed the highest propensity to label intracellular β 2 ARs in HEK293 T cell expressing exogenous β 2 ARs. This suggests that a combination of the polyethylene glycol (PEG) linker and the BODIPY‐X‐630/650 makes this ICI 118,551 derivative particularly susceptible to crossing the cell membrane to access the intracellular β 2 ARs. We have also used these ligands in combination with CRISPR/Cas9 genome‐edited HEK293 T cells to undertake for the first time real‐time ligand binding to native HEK293 T β 2 ARs at low native receptor expression levels. These studies provided quantitative data on ligand‐binding characteristics but also allowed real‐time visualization of the ligand‐binding interactions in genome‐edited cells using NanoBRET luminescence imaging.
Publisher: Elsevier BV
Date: 03-2001
Publisher: Wiley
Date: 02-2010
Publisher: American Chemical Society (ACS)
Date: 23-04-2018
DOI: 10.1021/ACS.JMEDCHEM.7B01565
Abstract: Recently, a novel negative allosteric modulator (NAM) of the D
Publisher: Wiley
Date: 24-05-2005
Publisher: American Chemical Society (ACS)
Date: 10-01-2018
DOI: 10.1021/ACS.JMEDCHEM.7B01811
Abstract: Opioids, like morphine, are the mainstay analgesics for the treatment and control of pain. Despite this, they often exhibit severe side effects that limit dose patients often become tolerant and dependent on these drugs, which remains a major health concern. The analgesic actions of opioids are primarily mediated via the μ-opioid receptor, a member of the G protein-coupled receptor superfamily. Thus far, development of small molecule fluorescent ligands for this receptor has resulted in antagonists, somewhat limiting the use of these probes. Herein, we describe our work on the development of a small molecule fluorescent probe based on the clinically used opiate morphine and initial characterization of its behavior in cell-based assays.
Publisher: American Chemical Society (ACS)
Date: 16-12-2015
DOI: 10.1021/ACS.JMEDCHEM.5B01664
Abstract: Fluorescently labeled ligands are useful pharmacological research tools for studying receptor localization, trafficking, and signaling processes via fluorescence imaging. They are also employed in fluorescent binding assays. This study is centered on the design, synthesis, and pharmacological evaluation of fluorescent probes for the opioid receptors, for which relatively few non-peptidic fluorescent probes currently exist. The known μ-opioid receptor (MOR) partial agonist, buprenorphine, was structurally elaborated to include an amidoalkylamine linker moiety that was coupled with a range of fluorophores to afford new fluorescent probes. All compounds proved to be selective MOR antagonists. Confocal fluorescence microscopy studies revealed that the probe incorporating a sulfonated cyanine-5 fluorophore was the most appropriate for imaging studies. This ligand was subsequently employed in an automated fluorescence-based competition binding assay, allowing the pKi values of several well-known opioid ligands to be determined. Thus, this new probe will prove useful in future studies of MOR receptor pharmacology.
Publisher: Elsevier BV
Date: 02-2001
Publisher: American Chemical Society (ACS)
Date: 16-03-2021
Publisher: Elsevier BV
Date: 09-1997
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1BM01548F
Abstract: Hyperbranched polyHPMA materials penetrate deep into pancreatic cancer spheroids and a hyperbranched polymer-gemcitabine conjugate showed potency in vitro and in vivo .
Publisher: International Union of Crystallography (IUCr)
Date: 19-11-2014
DOI: 10.1107/S205322961402436X
Abstract: Bicycle ring closure on a mixture of (4a S ,8a R )- and (4a R ,8a S )-ethyl 2-oxodecahydro-1,6-naphthyridine-6-carboxylate, followed by conversion of the separated cis and trans isomers to the corresponding thioamide derivatives, gave (4a SR ,8a RS )-ethyl 2-sulfanylidenedecahydro-1,6-naphthyridine-6-carboxylate, C 11 H 18 N 2 O 2 S. Structural analysis of this thioamide revealed a structure with two crystallographically independent conformers per asymmetric unit ( Z ′ = 2). The reciprocal bicycle ring closure on (3a RS ,7a RS )-ethyl 2-oxooctahydro-1 H -pyrrolo[3,2- c ]pyridine-5-carboxylate, C 10 H 16 N 2 O 3 , was also accomplished in good overall yield. Here the five-membered ring is disordered over two positions, so that both enantiomers are represented in the asymmetric unit. The compounds act as key intermediates towards the synthesis of potential new polycyclic medicinal chemical structures.
Publisher: Elsevier BV
Date: 02-1998
Publisher: Wiley
Date: 27-02-0027
DOI: 10.1111/BPH.12345
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Barrie Kellam.