2-Fluoro-ATP as a versatile tool for 19F NMR-based activity screening

Journal of the American Chemical Society
Brian J Stockman

Abstract

19F NMR-based methods have found utility in activity-based screening assays. However, because enzymes catalyze a diverse set of reactions, a large variety of fluorinated substrates would need to be identified to target each one separately. We have developed a more streamlined approach that is applicable to many enzymes that utilize ATP as a substrate. In this method, a fluorine-containing ATP analogue, 2-fluoro-ATP, is used to monitor the reaction. Applications are described for nicotinamide adenine dinucleotide synthetase and 3-phosphoinositide dependent kinase-1. Fragment screening results for the latter indicate that this technique can identify compounds that inhibit as well as activate reactions. The present results, together with previous biochemical studies from other laboratories, have shown that 2-fluoro-ATP can serve as a substrate for nine enzymes that are representative of three of the six enzyme subclasses, namely the transferases, hydrolases, and ligases. This suggests that 2-fluoro-ATP is suitable as a universal tool for screening ATP-requiring enzymes. Importantly, 2-fluoro-ATP has been determined to be a valid substrate for a variety of kinases, including both small molecule and protein kinases, suggesting that ...Continue Reading

References

Feb 1, 1983·Canadian Journal of Biochemistry and Cell Biology = Revue Canadienne De Biochimie Et Biologie Cellulaire·J H BaldoB D Sykes
Dec 10, 2002·Combinatorial Chemistry & High Throughput Screening·Claudio DalvitBrian J Stockman
Jun 19, 2003·Journal of the American Chemical Society·Claudio DalvitBrian J Stockman
Nov 20, 2003·Journal of the American Chemical Society·Claudio DalvitMarina Veronesi
Feb 27, 2004·Organic & Biomolecular Chemistry·Tobias TengelJan Kihlberg
Sep 24, 2004·Journal of the American Chemical Society·Lincoln G ScottMirko Hennig
Mar 24, 2007·Journal of Biomolecular Screening·Brian J StockmanZhi Xie

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Citations

Aug 20, 2011·Journal of the American Chemical Society·Koya YamaguchiShinsuke Sando
Apr 27, 2013·Chemical Communications : Chem Comm·Haiying GanBradley D Smith
Jul 23, 2014·Journal of the American Chemical Society·Yanchuan ZhaoTimothy M Swager
Jun 13, 2012·Chembiochem : a European Journal of Chemical Biology·Mika ItoHiroshi Abe
Feb 6, 2020·The Journal of Biological Chemistry·Warintra PitsawongAnne-Frances Miller
Aug 7, 2013·Chembiochem : a European Journal of Chemical Biology·Chiara LambruschiniClaudio Dalvit
Dec 18, 2013·ChemMedChem·Marina VeronesiClaudio Dalvit
Apr 30, 2020·Journal of Biomolecular NMR·Claudio DalvitAnna Vulpetti
Oct 31, 2013·Chemical Communications : Chem Comm·Tomohiro DouraShinsuke Sando
Mar 31, 2015·The Journal of Organic Chemistry·Marek R BaranowskiJacek Jemielity
Jun 30, 2019·Organic Letters·Huan MengYanchuan Zhao
Oct 9, 2018·Journal of Medicinal Chemistry·Claudio Dalvit, Anna Vulpetti
Aug 7, 2018·Chemical Reviews·Zhenchuang XuYanchuan Zhao
Nov 6, 2021·Chembiochem : a European Journal of Chemical Biology·Emmanuelle DevillersJulien Pytkowicz

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