Phosphorylation of Nucleoside-Metallacarborane and Carborane Conjugates by Nucleoside Kinases

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.

Keywords:

• Carborane
• metallacarborane
• nucleoside conjugates
• nucleoside kinase
• phosphorylation

Acknowledgments

This work was supported in part through funding from the Swedish Research Council to S. Eriksson and by the Polish Ministry of Science and Higher Education, Grant No K152/H03/2007/9 to B. Wojtczak, A. Olejniczak and Z. Leśnikowski.