Search Results - "Wrigley, Jonathan D"

BE-FLARE: a fluorescent reporter of base editing activity reveals editing characteristics of APOBEC3A and APOBEC3B by Coelho, Matthew A, Li, Songyuan, Pane, Luna Simona, Firth, Mike, Ciotta, Giovanni, Wrigley, Jonathan D, Cuomo, Maria Emanuela, Maresca, Marcello, Taylor, Benjamin J M

“…Base Editing is a precise genome editing method that uses a deaminase-Cas9 fusion protein to mutate cytidine to thymidine in target DNA in situ without the…”
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Mapping the sugar dependency for rational generation of a DNA-RNA hybrid-guided Cas9 endonuclease by Rueda, Fernando Orden, Bista, Michal, Newton, Matthew D., Goeppert, Anne U., Cuomo, M. Emanuela, Gordon, Euan, Kröner, Felix, Read, Jon A., Wrigley, Jonathan D., Rueda, David, Taylor, Benjamin J. M.

“…The CRISPR–Cas9 RNA-guided endonuclease system allows precise and efficient modification of complex genomes and is continuously developed to enhance…”
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Identification and Characterization of Dual Inhibitors of the USP25/28 Deubiquitinating Enzyme Subfamily by Wrigley, Jonathan D, Gavory, Gerald, Simpson, Iain, Preston, Marian, Plant, Helen, Bradley, Jenna, Goeppert, Anne U, Rozycka, Ewelina, Davies, Gareth, Walsh, Jarrod, Valentine, Andrea, McClelland, Keeva, Odrzywol, Krzysztofa Ewa, Renshaw, Jonathan, Boros, Joanna, Tart, Jonathan, Leach, Lindsey, Nowak, Thorsten, Ward, Richard A, Harrison, Timothy, Andrews, David M

“…The ubiquitin proteasome system is widely postulated to be a new and important field of drug discovery for the future, with the ubiquitin specific proteases…”
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Novel Orally Bioavailable γ-Secretase Inhibitors with Excellent in Vivo Activity by Keown, Linda E, Collins, Ian, Cooper, Laura C, Harrison, Timothy, Madin, Andrew, Mistry, Jayesh, Reilly, Michael, Shaimi, Mohamed, Welch, Christopher J, Clarke, Earl E, Lewis, Huw D, Wrigley, Jonathan D. J, Best, Jonathan D, Murray, Fraser, Shearman, Mark S

“…The development of potent γ-secretase inhibitors having substituted heterocycles attached to a benzobicyclo[4.2.1]nonane core is described. This work led to…”
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In Vitro Characterization of the Presenilin-Dependent γ-Secretase Complex Using a Novel Affinity Ligand by Beher, Dirk, Fricker, Michael, Nadin, Alan, Clarke, Earl E, Wrigley, Jonathan D. J, Li, Yue-Ming, Culvenor, Janetta G, Masters, Colin L, Harrison, Timothy, Shearman, Mark S

“…γ-Secretase is the enzyme activity releasing the amyloid-β peptide from membrane-bound processing intermediates derived from the β-amyloid precursor protein…”
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Design and Synthesis of Highly Potent Benzodiazepine γ-Secretase Inhibitors:  Preparation of (2S,3R)-3-(3,4- Difluorophenyl)-2-(4-fluorophenyl)-4- hydroxy-N-((3S)-1-methyl-2-oxo-5- phenyl-2,3-dihydro-1H-benzo[e][1,4]- diazepin-3-yl)butyramide by Use of an Asymmetric Ireland−Claisen Rearrangement by Churcher, Ian, Williams, Susie, Kerrad, Sonia, Harrison, Timothy, Castro, José L, Shearman, Mark S, Lewis, Huw D, Clarke, Earl E, Wrigley, Jonathan D. J, Beher, Dirk, Tang, Yui S, Liu, Wensheng

“…Novel benzodiazepine-containing γ-secretase inhibitors for potential use in Alzheimer's disease have been designed that incorporate a substituted…”
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Intra- or Intercomplex Binding to the γ-Secretase Enzyme: A MODEL TO DIFFERENTIATE INHIBITOR CLASSES by Clarke, Earl E, Churcher, Ian, Ellis, Semantha, Wrigley, Jonathan D.J, Lewis, Huw D, Harrison, Timothy, Shearman, Mark S, Beher, Dirk

“…γ-Secretase is one of the critical enzymes required for the generation of amyloid-β peptides from the β-amyloid precursor protein. Because amyloid-β peptides…”
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3-Substituted gem-cyclohexane sulfone based γ-secretase inhibitors for Alzheimer’s disease: Conformational analysis and biological activity by Jelley, Richard A., Elliott, Jason, Gibson, Karl R., Harrison, Timothy, Beher, Dirk, Clarke, Earl E., Lewis, Huw D., Shearman, Mark, Wrigley, Jonathan D.J.

“…The synthesis, biological activity and conformational analysis of 3-substituted gem-cyclohexanes based on 1 have provided compounds with high γ-secretase…”
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Conserved residues within the putative active site of γ‐secretase differentially influence enzyme activity and inhibitor binding by Wrigley, Jonathan D. J., Nunn, Emma J., Nyabi, Omar, Clarke, Earl E., Hunt, Peter, Nadin, Alan, De Strooper, Bart, Shearman, Mark S., Beher, Dirk

“…γ‐Secretase performs the final processing step in the generation of amyloid‐β (Aβ) peptides, which are believed to be causative for Alzheimer's disease…”
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Cell banking for pharmaceutical research by Wrigley, Jonathan D., McCall, Eileen J., Bannaghan, Claire L., Liggins, Laura, Kendrick, Clare, Griffen, Alison, Hicks, Ryan, Fröderberg-Roth, Linda

“…•We describe the current challenges, practices and opportunities within cell banking.•A centralised cell banking model employed within AstraZeneca is…”
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Selected non-steroidal anti-inflammatory drugs and their derivatives target gamma-secretase at a novel site. Evidence for an allosteric mechanism by Beher, Dirk, Clarke, Earl E, Wrigley, Jonathan D J, Martin, Agnes C L, Nadin, Alan, Churcher, Ian, Shearman, Mark S

“…Gamma-secretase is a multi-component enzyme complex that performs an intramembranous cleavage, releasing amyloid-beta (Abeta) peptides from processing…”
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Generation of C‐terminally truncated amyloid‐β peptides is dependent on γ‐secretase activity by Beher, Dirk, Wrigley, Jonathan D. J., Owens, Andrew P., Shearman, Mark S.

“…Aberrant production of amyloid‐β peptides by processing of the β‐amyloid precursor protein leads to the formation of characteristic extracellular protein…”
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Enzymatic Characterisation of USP7 Deubiquitinating activity and Inhibition by Wrigley, Jonathan D., Eckersley, Kay, Hardern, Ian M., Millard, Lindsey, Walters, Michael, Peters, Stephen W., Mott, Richard, Nowak, Thorsten, Ward, Richard A., Simpson, Peter B., Hudson, Kevin

“…USP7 (HAUSP) is a deubiquitinating enzyme, which plays a crucial role in regulating the levels of the p53 tumour suppressor protein, through its ability to…”
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4-Substituted cyclohexyl sulfones as potent, orally active γ-secretase inhibitors by Churcher, Ian, Beher, Dirk, Best, Jonathan D., Castro, José L., Clarke, Earl E., Gentry, Amy, Harrison, Timothy, Hitzel, Laure, Kay, Euan, Kerrad, Sonia, Lewis, Huw D., Morentin-Gutierrez, Pablo, Mortishire-Smith, Russell, Oakley, Paul J., Reilly, Michael, Shaw, Duncan E., Shearman, Mark S., Teall, Martin R., Williams, Susie, Wrigley, Jonathan D.J.

“…Studies leading to the identification of the orally active γ-secretase inhibitor 32 are described. This compound demonstrated lowering of central Aβ(40) in a…”
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A new series of potent benzodiazepine γ-secretase inhibitors by Churcher, Ian, Ashton, Kate, Butcher, John W., Clarke, Earl E., Harrison, Timothy, Lewis, Huw D., Owens, Andrew P., Teall, Martin R., Williams, Susie, Wrigley, Jonathan D.J.

“…A new series of benzodiazepine-containing γ-secretase inhibitors with potential use in the treatment of Alzheimer's disease is disclosed. Structure–activity…”
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High affinity, bioavailable 3-Amino-1,4-benzodiazepine-Based γ-Secretase inhibitors by Owens, Andrew P., Nadin, Alan, Talbot, Adam C., Clarke, Earl E., Harrison, Timothy, Lewis, Huw D., Reilly, Michael, Wrigley, Jonathan D.J., Castro, José L.

“…In this paper, we describe the development of a novel series of high affinity, orally bioavailable 3-amino-1,4 benzodiazepine-based γ-secretase inhibitors for…”
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Functional Overexpression of γ-Secretase Reveals Protease-independent Trafficking Functions and a Critical Role of Lipids for Protease Activity by Wrigley, Jonathan D.J., Schurov, Irina, Nunn, Emma J., Martin, Agnes C.L., Clarke, Earl E., Ellis, Semantha, Bonnert, Timothy P., Shearman, Mark S., Beher, Dirk

“…Presenilins appear to form the active center of γ-secretase but require the presence of the integral membrane proteins nicastrin, anterior pharynx defective 1,…”
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Abstract 4043: Characterization of the enzymatic activity, biochemical requirements and inhibition of deubiquitinating enzymes, a novel oncology target class by Wrigley, Jonathan D., Eckersley, Kay, Plant, Helen, Preston, Marian, Millard, Lindsey, Hardern, Ian, Nowak, Thorsten, Simpson, Peter B., Andrews, David, Hudson, Kevin

“…Abstract Deubiquitinating enzymes (DUBs) represent promising opportunities for therapeutic intervention in oncology, and this study reports key information…”
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The geminal dimethyl analogue of Flurbiprofen as a novel Aβ42 inhibitor and potential Alzheimer's disease modifying agent by STOCK, Nicholas, MUNOZ, Benito, ST-JACQUES, René, PRASIT, Peppi, WRIGLEY, Jonathan D. J, SHEARMAN, Mark S, BEHER, Dirk, PEACHEY, James, WILLIAMSON, Toni L, BAIN, Gretchen, WEICHAO CHEN, XIAOHUI JIANG

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Methionine-rich repeat proteins: a family of membrane-associated proteins which contain unusual repeat regions by Weiss, Jamie L., Evans, Nicholas A., Ahmed, Tanweer, Wrigley, Jonathan D.J., Khan, Shukria, Wright, Charles, Keen, Jeffrey N., Holzenburg, Andreas, Findlay, John B.C.

“…We report the protein isolation, cloning and characterization of members of an unusual protein family, which comprise the most abundant proteins present in the…”
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