A Photoreactive Small-Molecule Probe for 2-Oxoglutarate Oxygenases

Rotili, Dante; Mikael, Altun; Akane, Kawamura; Alexander, Wolf; Roman, Fischer; Leung, I. k.; Mukram m, Mackeen; Ya Min Tian,; Peter j, Ratcliffe; Mai, Antonello; Benedikt m, Kessler; Christopher j, Schofield

doi:10.1016/j.chembiol.2011.03.007

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.

A Photoreactive Small-Molecule Probe for 2-Oxoglutarate Oxygenases / Rotili, Dante; Mikael, Altun; Akane, Kawamura; Alexander, Wolf; Roman, Fischer; I. k., Leung; Mukram m, Mackeen; Ya Min, Tian; Peter j, Ratcliffe; Mai, Antonello; Benedikt m, Kessler; Christopher j, Schofield. - In: CHEMISTRY & BIOLOGY. - ISSN 1074-5521. - 18:5(2011), pp. 642-654.

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Titolo:	A Photoreactive Small-Molecule Probe for 2-Oxoglutarate Oxygenases
Autori:	ROTILI, Dante Mikael Altun Akane Kawamura Alexander Wolf Roman Fischer I. k. Leung Mukram m Mackeen Ya Min Tian Peter j Ratcliffe MAI, Antonello Benedikt m Kessler Christopher j Schofield mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2011
Rivista:	CHEMISTRY & BIOLOGY
Citazione:	A Photoreactive Small-Molecule Probe for 2-Oxoglutarate Oxygenases / Rotili, Dante; Mikael, Altun; Akane, Kawamura; Alexander, Wolf; Roman, Fischer; I. k., Leung; Mukram m, Mackeen; Ya Min, Tian; Peter j, Ratcliffe; Mai, Antonello; Benedikt m, Kessler; Christopher j, Schofield. - In: CHEMISTRY & BIOLOGY. - ISSN 1074-5521. - 18:5(2011), pp. 642-654.
Handle:	http://hdl.handle.net/11573/442882
Appartiene alla tipologia:	01a Articolo in rivista

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