Journal article
Fluorination influences the bioisostery of myo-inositol pyrophosphate analogs
- Abstract:
- Inositol pyrophosphates (PP-IPs) are densely phosphorylated messenger molecules involved in numerous biological processes. PP-IPs contain one or two pyrophosphate group(s) attached to a phosphorylated myo-inositol ring. 5PP-IP5 is the most abundant PP-IP in human cells. To investigate the function and regulation by PP-IPs in biological contexts, metabolically stable analogs have been developed. Here, we report the synthesis of a new fluorinated phosphoramidite reagent and its application for the synthesis of a difluoromethylene bisphosphonate analog of 5PP-IP5. Subsequently, the properties of all currently reported analogs were benchmarked using a number of biophysical and biochemical methods, including co-crystallization, ITC, kinase activity assays and chromatography. Together, the results showcase how small structural alterations of the analogs can have notable effects on their properties in a biochemical setting and will guide in the choice of the most suitable analog(s) for future investigations.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.0MB, Terms of use)
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- Publisher copy:
- 10.1002/chem.202302426
Authors
- Publisher:
- Wiley
- Journal:
- Chemistry - A European Journal More from this journal
- Volume:
- 29
- Issue:
- 67
- Article number:
- e202302426
- Publication date:
- 2023-09-29
- Acceptance date:
- 2023-09-28
- DOI:
- EISSN:
-
1521-3765
- ISSN:
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0947-6539
- Language:
-
English
- Keywords:
- Pubs id:
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1545439
- Local pid:
-
pubs:1545439
- Deposit date:
-
2023-10-18
- ARK identifier:
Terms of use
- Copyright holder:
- Hostachy et al
- Copyright date:
- 2023
- Rights statement:
- © 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Notes:
- This research was funded in part, by the Wellcome Trust. For the purpose of Open Access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
- Licence:
- CC Attribution (CC BY)
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