Fluorination influences the bioisostery of myo-inositol pyrophosphate analogs
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 a...
| Main Authors: | , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
Wiley
2023
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| _version_ | 1826312251059994624 |
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| author | Hostachy, S Wang, H Zong, G Riley, AM Potter, BVL Fiedler, D |
| author_facet | Hostachy, S Wang, H Zong, G Riley, AM Potter, BVL Fiedler, D |
| author_sort | Hostachy, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T08:26:18Z |
| format | Journal article |
| id | oxford-uuid:7fbc6126-7e6c-4acb-aff4-4c5da921363b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:26:18Z |
| publishDate | 2023 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:7fbc6126-7e6c-4acb-aff4-4c5da921363b2024-02-16T08:39:36ZFluorination influences the bioisostery of myo-inositol pyrophosphate analogsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7fbc6126-7e6c-4acb-aff4-4c5da921363bEnglishSymplectic ElementsWiley2023Hostachy, SWang, HZong, GRiley, AMPotter, BVLFiedler, DInositol 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. |
| spellingShingle | Hostachy, S Wang, H Zong, G Riley, AM Potter, BVL Fiedler, D Fluorination influences the bioisostery of myo-inositol pyrophosphate analogs |
| title | Fluorination influences the bioisostery of myo-inositol pyrophosphate analogs |
| title_full | Fluorination influences the bioisostery of myo-inositol pyrophosphate analogs |
| title_fullStr | Fluorination influences the bioisostery of myo-inositol pyrophosphate analogs |
| title_full_unstemmed | Fluorination influences the bioisostery of myo-inositol pyrophosphate analogs |
| title_short | Fluorination influences the bioisostery of myo-inositol pyrophosphate analogs |
| title_sort | fluorination influences the bioisostery of myo inositol pyrophosphate analogs |
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