Synthesis of the first ferrocene-labeled dideoxynucleotide and its use for3 '-redox end-labeling of 5 '-modified single-stranded oligonucleotides

The target ferrocene-labeled dideoxynucleotide compound 5-[N-(beta -ferrace nyl-propanoyl)3-amino-propynl-yl] -2',3'-dideoxyuridine 5'-triphosphate, Fc -ddUTP, was synthesized and tested with terminal deoxynucleotidyl transfera se for enzymatic S'-redox-active end-labeling of 5'-phosphorylated single-s tranded oligodeoxynucleotides. Starting from readily available 5-iodouridin e and 3-ferrocenylpropanoic acid, the synthetic strategy elaborated here fo llows a mild multistep route. Each step involves reliable methods, and all ferrocene intermediates can be easily purified. Enzymatic 3'-ferrocene end- labeling of 5'-phosphorylated oligonucleotides is remarkably efficient, and 3'-ferrocene-labeled oligonucleotides can thus be prepared in sufficient a mounts for further use in surface modifications.