Alkylation of staurosporine to derive a kinase probe for fluorescence applications

Disney, Alexander J.M. and Kellam, Barrie and Dekker, Lodewijk V. (2016) Alkylation of staurosporine to derive a kinase probe for fluorescence applications. ChemMedChem, 11 . pp. 972-979. ISSN 1860-7187

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Abstract

The natural product staurosporine is a high-affinity inhibitor of nearly all mammalian protein kinases.The labelling of staurosporine has proven effective as a means of generating protein kinase research tools. Most tools have been generated by acylation of the 4’-methylamine of the sugar moiety of staurosporine. Herein we describe the alkylation of this group as a first step to generate a fluorescently labelled staurosporine. Following alkylation, a polyethylene glycol linker was installed, allowing subsequent attachment of fluorescein. We report that this fluorescein–staurosporine conjugate binds to cAMP-dependent protein kinase in the nanomolar range. Furthermore, its binding can be antagonised with unmodified staurosporine as well as ATP, indicating it targets the ATP binding site in a similar fashion to native staurosporine. This reagent has potential application as a screening tool for protein kinases of interest.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: 10.1002/cmdc.201500589
Depositing User: Dekker, Lodewijk
Date Deposited: 27 Feb 2017 08:40
Last Modified: 13 Oct 2017 04:26
URI: http://eprints.nottingham.ac.uk/id/eprint/40837

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