title: Rational Development of Novel Activity Probes for the Analysis of Human Cytochromes P450.
abstract: The identification and quantification of functional cytochromes P450 (CYPs) in biological samples is proving important for robust analyses of drug efficacy and metabolic disposition. In this study, a novel CYP activity-based probe was rationally designed and synthesised, demonstrating selective binding of CYP isoforms. The dependence of probe binding upon the presence of NADPH permits the selective detection of functionally active CYP. This allows the detection and analysis of these enzymes using biochemical and proteomic methodologies and approaches.
authors.affiliation: School of Medicine, Pharmacy and Health, Durham University, Queen's Campus, University Boulevard, Stockton-on-Tees, TS17 6BH, UK. j.d.sellars@durham.ac.uk.
authors.forename: Jonathan D
authors.identifier: 0000-0003-1430-012X
authors.initials: JD
authors.lastname: Sellars
authors.affiliation: School of Medicine, Pharmacy and Health, Durham University, Queen's Campus, University Boulevard, Stockton-on-Tees, TS17 6BH, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Skipsey
authors.affiliation: The Institute of Cancer Therapeutics, University of Bradford, West Yorkshire, BD7 1DP, UK.
authors.lastname: Sadr-Ul-Shaheed
authors.affiliation: The Institute of Cancer Therapeutics, University of Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gravell
authors.affiliation: The Institute of Cancer Therapeutics, University of Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Hamza
authors.initials: H
authors.lastname: Abumansour
authors.affiliation: The Institute of Cancer Therapeutics, University of Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Ghasaq
authors.initials: G
authors.lastname: Kashtl
authors.affiliation: The Institute of Cancer Therapeutics, University of Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Jawaria
authors.initials: J
authors.lastname: Irfan
authors.affiliation: The Institute of Cancer Therapeutics, University of Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Khot
authors.affiliation: The Institute of Cancer Therapeutics, University of Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pors
authors.affiliation: The Institute of Cancer Therapeutics, University of Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Patterson
authors.affiliation: The Institute of Cancer Therapeutics, University of Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Chris W
authors.initials: CW
authors.lastname: Sutton
mesh_terms: D001572:Benzofurans / Q000737:chemistry / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D013058:Mass Spectrometry; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D040901:Proteomics
chemical_list: D001572:Benzofurans; D015335:Molecular Probes; D020033:Protein Isoforms; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; C105430:benzofuran
keywords: activity-based probes; benzofuran; cytochrome P450; protein profiling; proteomics