F-ara-AMP is a substrate of cytoplasmic 5'-nucleotidase II (cN-II): HPLC and NMR studies of enzymatic dephosphorylation

Nucleosides, Nucleotides & Nucleic Acids
Lars Petter JordheimMarie-Claude Gagnieu

Abstract

Intracellular accumulation of triphosphorylated derivatives is essential for the cytotoxic activity of nucleoside analogues. Different mechanisms opposing this accumulation have been described. We have investigated the dephosphorylation of monophosphorylated fludarabine (F-ara-AMP) by the purified cytoplasmic 5'-nucleotidase cN-II using HPLC and NMR. These studies clearly showed that cN-II was able to convert F-ara-AMP into its non phosphorylated form, F-ara-A, with a Km in the millimolar range and Vmax = 35 nmol/min/mg, with both methods. Cytoplasmic 5'-nucleotidase cN-II can degrade this clinically useful cytotoxic nucleoside analogue and its overexpression is thus likely to be involved in resistance to this compound.

References

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Oct 1, 1989·Molecular and Biochemical Parasitology·H M Meadows, A J Simpson
Mar 15, 1996·The Biochemical Journal·A C SkladanowskiW Makarewicz
Jul 18, 2003·Current Drug Targets·L JordheimC Dumontet

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Citations

Nov 26, 2015·Journal of Medicinal Chemistry·Zsuzsanna MartonLaurent Chaloin
Jun 19, 2010·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Sabine CohenJérôme Guitton
Nov 29, 2015·Cancer Chemotherapy and Pharmacology·Chiara RampazzoLars Petter Jordheim
Mar 18, 2015·Bioorganic & Medicinal Chemistry·Kayla M BorlandVladislav A Litosh
May 1, 2008·Biochimica Et Biophysica Acta·Maria Giovanna CaredduMaria Grazia Tozzi
Feb 7, 2015·Biochemical Pharmacology·F CividiniM G Tozzi

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Methods Mentioned

BETA
nuclear magnetic resonance
NMR

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Chromquest
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