A photoreactive small-molecule probe for 2-oxoglutarate oxygenases.
2-oxoglutarate (2-OG)-dependent oxygenases have diverse roles in human biology. The inhibition of several 2-OG oxygenases is being targeted for therapeutic intervention, including for cancer, anemia, and ischemic diseases. We report a small-molecule probe for 2-OG oxygenases that employs a hydroxyqu...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1797079698899992576 |
|---|---|
| author | Rotili, D Altun, M Kawamura, A Wolf, A Fischer, R Leung, I Mackeen, M Tian, Y Ratcliffe, P Mai, A Kessler, B Schofield, C |
| author_facet | Rotili, D Altun, M Kawamura, A Wolf, A Fischer, R Leung, I Mackeen, M Tian, Y Ratcliffe, P Mai, A Kessler, B Schofield, C |
| author_sort | Rotili, D |
| collection | OXFORD |
| description | 2-oxoglutarate (2-OG)-dependent oxygenases have diverse roles in human biology. The inhibition of several 2-OG oxygenases is being targeted for therapeutic intervention, including for cancer, anemia, and ischemic diseases. We report a small-molecule probe for 2-OG oxygenases that employs a hydroxyquinoline template coupled to a photoactivable crosslinking group and an affinity-purification tag. Following studies with recombinant proteins, the probe was shown to crosslink to 2-OG oxygenases in human crude cell extracts, including to proteins at endogenous levels. This approach is useful for inhibitor profiling, as demonstrated by crosslinking to the histone demethylase FBXL11 (KDM2A) in HEK293T nuclear extracts. The results also suggest that small-molecule probes may be suitable for substrate identification studies. |
| first_indexed | 2024-03-07T00:49:29Z |
| format | Journal article |
| id | oxford-uuid:85e4072a-642a-4609-9468-5fa804c8707e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:49:29Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:85e4072a-642a-4609-9468-5fa804c8707e2022-03-26T22:00:28ZA photoreactive small-molecule probe for 2-oxoglutarate oxygenases.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:85e4072a-642a-4609-9468-5fa804c8707eEnglishSymplectic Elements at Oxford2011Rotili, DAltun, MKawamura, AWolf, AFischer, RLeung, IMackeen, MTian, YRatcliffe, PMai, AKessler, BSchofield, C2-oxoglutarate (2-OG)-dependent oxygenases have diverse roles in human biology. The inhibition of several 2-OG oxygenases is being targeted for therapeutic intervention, including for cancer, anemia, and ischemic diseases. We report a small-molecule probe for 2-OG oxygenases that employs a hydroxyquinoline template coupled to a photoactivable crosslinking group and an affinity-purification tag. Following studies with recombinant proteins, the probe was shown to crosslink to 2-OG oxygenases in human crude cell extracts, including to proteins at endogenous levels. This approach is useful for inhibitor profiling, as demonstrated by crosslinking to the histone demethylase FBXL11 (KDM2A) in HEK293T nuclear extracts. The results also suggest that small-molecule probes may be suitable for substrate identification studies. |
| spellingShingle | Rotili, D Altun, M Kawamura, A Wolf, A Fischer, R Leung, I Mackeen, M Tian, Y Ratcliffe, P Mai, A Kessler, B Schofield, C A photoreactive small-molecule probe for 2-oxoglutarate oxygenases. |
| title | A photoreactive small-molecule probe for 2-oxoglutarate oxygenases. |
| title_full | A photoreactive small-molecule probe for 2-oxoglutarate oxygenases. |
| title_fullStr | A photoreactive small-molecule probe for 2-oxoglutarate oxygenases. |
| title_full_unstemmed | A photoreactive small-molecule probe for 2-oxoglutarate oxygenases. |
| title_short | A photoreactive small-molecule probe for 2-oxoglutarate oxygenases. |
| title_sort | photoreactive small molecule probe for 2 oxoglutarate oxygenases |
| work_keys_str_mv | AT rotilid aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT altunm aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT kawamuraa aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT wolfa aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT fischerr aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT leungi aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT mackeenm aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT tiany aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT ratcliffep aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT maia aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT kesslerb aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT schofieldc aphotoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT rotilid photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT altunm photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT kawamuraa photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT wolfa photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT fischerr photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT leungi photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT mackeenm photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT tiany photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT ratcliffep photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT maia photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT kesslerb photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases AT schofieldc photoreactivesmallmoleculeprobefor2oxoglutarateoxygenases |