Phosphorylation of Nucleoside-Metallacarborane and Carborane Conjugates by Nucleoside Kinases |
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Authors: | Blazej A Wojtczak Agnieszka B Olejniczak Liya Wang Staffan Eriksson Zbigniew J Lesnikowski |
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Institution: | 1. Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences , Lodz , Poland;2. Division of Biophysics, Institute of Experimental Physics, University of Warsaw , Zwirki i Wigury 93, 02-089 , Warsaw , Poland;3. Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences , Lodz , Poland;4. Department of Anatomy , Physiology and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Center , Uppsala , Sweden |
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Abstract: | A library of purine and pyrimidine nucleosides modified with carborane or metallacarborane boron clusters at different locations, consisting of new molecules as well as already described compounds, was prepared. The compounds were tested as substrates for human deoxynucleoside kinases. Some conjugates, with modification attached to N3 of thymidine via a linker containing the triazole moiety, were efficiently phosphorylated by cytosolic thymidine kinase 1 and mitochondrial thymidine kinase 2. Higher phosphorylation levels were observed with thymidine kinase 1, the phosphorylation of nucleosides modified with metallacarboranes was observed for the first time. |
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Keywords: | Carborane metallacarborane nucleoside conjugates nucleoside kinase phosphorylation |
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