| Literature DB >> 21609845 |
Akane Kawamura1, Alexander Wolf1, Dante Rotili1,2, Mikael Altun3, Roman Fischer3, Ivanhoe K H Leung1, Mukram M Mackeen3, Ya-Min Tian3, Peter J Ratcliffe3, Antonello Mai2, Benedikt M Kessler3, Christopher J Schofield1.
Abstract
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.Entities:
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Year: 2011 PMID： 21609845 PMCID： PMC4681097 DOI： 10.1016/j.chembiol.2011.03.007
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521