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A novel class of fluorinated A2A adenosine receptor agonist with application to last step enzymatic [18F]fluorination for PET imaging

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O_Hagan_2017_ChemBioChem_A2Aadenosine_AAM.pdf (1.637Mb)
Date
02/11/2017
Author
Lowe, Phillip T.
Dall'Angello, Sergio
Mulder-Krieger, Thea
Ijzerman, Adriaan P.
Zanda, Matteo
O'Hagan, David
Keywords
Adenosine receptors
Biocatalysis
Fluorinase
18F labelling
Positron emission tomography
QD Chemistry
QH301 Biology
NDAS
Metadata
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Abstract
The A2A adenosine receptor belongs to a family of G-coupled protein receptors that have been subjected to extensive investigation over the last few decades. Due to their prominent role in the biological functions of the heart, lungs, CNS and brain, they have become a target for the treatment of illnesses ranging from cancer immunotherapy to Parkinson's disease. The imaging of such receptors using positron emission tomography (PET) has also been of interest, potentially providing a valuable tool to analyse and diagnose various myocardial and neurodegenerative disorders, as well as offering support to drug discovery trials. Reported herein is the design, synthesis and evaluation of two novel 5'-fluorodeoxy-adenosine (FDA) based receptor agonists (FDA-PP1 and FDA-PP2), each substituted at the C-2 position with a terminally functionalised ethynyl unit. The structures enable a synthesis of 18F-labelled analogues via direct, last-step, radiosynthesis from chlorinated precursors using the fluorinase enzyme (5'-fluoro-5'-deoxyadenosine synthase) which catalyses a transhalogenation reaction. This delivers a new class of A2A adenosine receptor agonist which can be directly radiolabelled for exploration in PET studies.
Citation
Lowe , P T , Dall'Angello , S , Mulder-Krieger , T , Ijzerman , A P , Zanda , M & O'Hagan , D 2017 , ' A novel class of fluorinated A 2A adenosine receptor agonist with application to last step enzymatic [ 18 F]fluorination for PET imaging ' , ChemBioChem , vol. 18 , no. 21 , pp. 2156-2164 . https://doi.org/10.1002/cbic.201700382
Publication
ChemBioChem
Status
Peer reviewed
DOI
https://doi.org/10.1002/cbic.201700382
ISSN
1439-7633
Type
Journal article
Rights
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1002/cbic.201700382
Description
The authors thank the Engineering and Physical Sciences Research Council, UK, for a research grant.
Collections
  • University of St Andrews Research
URL
http://onlinelibrary.wiley.com/doi/10.1002/cbic.201700382/full#footer-support-info
URI
http://hdl.handle.net/10023/16056

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