Nucleotide analogues with modifications on 5'-triphosphate fragment have been extensively used as probes for examination of functions and structures of enzymes that are overexpressed in cancer cells. However, the ionic character of phosphate functionality leads to the lack in membrane permeability; therefore phosphate containing molecules usually are not perfect biologic probes. Thus discovery of the appropriate phosphate mimics are very important for finding enzyme inhibitors. Towards this endeavor the synthesis of new nonhydrolysable nucleotide analogues in which phosphate is replaced by squaric acid moiety has been attempted. Moreover substitution of the bridging oxygen atom in a, � or �, ? positions of triphosphoric acid with the CH2 and CF2 group provides increasing stability toward enzymatic hydrolysis. Additionally introduction of squaric acid into triphosphate analogue could potentially reveal new interaction with the active sites not present in the case of natural nucleotide triphosphates.

Synthesis and biological evaluation of nonhydrolyzable nucleotide analogs based on squaric acid

244th National Meeting (2012)

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