Rational Development of Novel Activity Probes for the Analysis of Human Cytochromes P450

Sellars, Jonathan D.; Skipsey, Mark; Shaheed, Sadr-ul; Gravell, Sebastian; Abumansour, Hamza; Kashtl, Ghasaq; Irfan, Jawaria; Khot, Mohamed; Pors, Klaus; Patterson, Laurence H.; Sutton, Chris W.

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.

Citation

Sellars, J. D., Skipsey, M., Shaheed, S., Gravell, S., Abumansour, H., Kashtl, G., …Sutton, C. W. (2016). Rational Development of Novel Activity Probes for the Analysis of Human Cytochromes P450. ChemMedChem, 11(11), 1122-1128. https://doi.org/10.1002/cmdc.201600134

• Journal Article Type: Article
• Online Publication Date: May 6, 2016
• Publication Date: Jun 6, 2016
• Deposit Date: Jun 23, 2016
• Publicly Available Date: May 6, 2017
• Journal: ChemMedChem
• Print ISSN: 1860-7179
• Electronic ISSN: 1860-7187
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 11
• Pages: 1122-1128
• DOI: https://doi.org/10.1002/cmdc.201600134