Explore the words cloud of the PCAGED-KI project. It provides you a very rough idea of what is the project "PCAGED-KI" about.
The following table provides information about the project.
Coordinator |
GOETEBORGS UNIVERSITET
Organization address contact info |
Coordinator Country | Sweden [SE] |
Project website | http://grotlilab.net/research/photopharmacology/kinase-inhibitors/ |
Total cost | 173˙857 € |
EC max contribution | 173˙857 € (100%) |
Programme |
1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility) |
Code Call | H2020-MSCA-IF-2016 |
Funding Scheme | MSCA-IF-EF-ST |
Starting year | 2017 |
Duration (year-month-day) | from 2017-10-01 to 2019-09-30 |
Take a look of project's partnership.
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1 | GOETEBORGS UNIVERSITET | SE (GOETEBORG) | coordinator | 173˙857.00 |
Protein kinases play a critical role in a number of cellular processes, including cell proliferation, differentiation and apoptosis. Recently, the aberrant regulation of lymphocyte-specific protein tyrosine kinases (LCK) has been associated with the over activation of microglia cells (important immune effector cells that reside in the central nervous system, CNS) and in turn, the development of Alzheimer’s disease (AD). Unfortunately, the detail of LCK's dynamic function and the importance of quantitative, spatial and time-dependent parameters regarding microglia activation is poorly understood. As such, the ability to manipulate LCK activity using light would result in temporal control of enzymatic activity, thus serving as a valuable approach to probe the function of LCK in microglia cells and in turn, further our understanding of AD and related neurodegenerative disorders. While such studies cannot be performed using conventional LCK inhibitors, this project aims to control the enzymatic activity of LCK by the development of a stimuli-responsive release-and-report system, through the introduction of a photolabile 'caging' moiety onto a fluorescent kinase inhibitor. The caging group will also consist of an appropriate ‘quencher’, quenching the innate fluorescence properties of the inhibitor through energy transfer (FRET). Exposure to light (> 320 nm) will result in decaging of the prodrug to give the active form, while simultaneously switching ‘on’ the fluorescence — reporting back to the user that the compound has been activated. To demonstrate the potential of the release-and-report kinase inhibitor as a tool to probe LCK function in microglia cells, confocal microscopy will be employed to visualise the site of microglia activation and the time frame during CNS development in zebrafish model systems.
year | authors and title | journal | last update |
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2019 |
Cassandra L. Fleming, Morten Grøtli, Joakim Andréasson Onâ€Command Regulation of Kinase Activity using Photonic Stimuli published pages: 318-326, ISSN: 2367-0932, DOI: 10.1002/cptc.201800253 |
ChemPhotoChem 3/6 | 2020-02-12 |
2018 |
Cassandra L. Fleming, Shiming Li, Morten Grøtli, Joakim Andréasson Shining New Light on the Spiropyran Photoswitch: A Photocage Decides between cis – trans or Spiro-Merocyanine Isomerization published pages: 14069-14072, ISSN: 0002-7863, DOI: 10.1021/jacs.8b09523 |
Journal of the American Chemical Society 140/43 | 2020-02-12 |
2019 |
Cassandra L. Fleming, Patrick A. Sandoz, Tord Inghardt, Björn Önfelt, Morten Grøtli, Joakim Andréasson A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding published pages: 15000-15004, ISSN: 1433-7851, DOI: 10.1002/anie.201909536 |
Angewandte Chemie International Edition 58/42 | 2020-02-12 |
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