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

We report here the synthesis of nucleoside and oligonucleotide analogs cont aining selenium, which serves as an anomalous scattering center to enable M AD phase determination in nucleotide X-ray crystallography. We have develop ed 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 sel enium functionality, the leaving groups (bromide, mesyl. and tosyl) were re adily displaced by sodium selenide, sodium diselenide, and sodium methyl se lenide with yields higher than 90%. Selenium-derivatized oligonucleotides h ave been synthesized via phosphoramidite chemistry.