Synthesis of selenium-derivatized nucleosides and oligonucleotides for X-ray crystallography

We report here the synthesis of nucleoside and oligonucleotide analogs containing selenium, which serves as an anomalous scattering center to enable MAD phase determination in nucleotide X-ray crystallography. We have developed a phase transfer approach to introduce the selenium functionality in A C G, T. and U nucleosides at 5 ' -positions. In the incorporation of the selenium functionality, the leaving groups (bromide, mesyl. and tosyl) were readily displaced by sodium selenide, sodium diselenide, and sodium methyl selenide with yields higher than 90%. Selenium-derivatized oligonucleotides have been synthesized via phosphoramidite chemistry.