SYNTHESIS OF SELENIUM-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOTIDES FOR X-RAY CRYSTALLOGRAPHY

Abstract

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.

ACKNOWLEDGMENT

This work was supported by PSC-CUNY Research Award (#69674) and New Faculty Awards. We thank Dr. Hsing Wang for collecting ⁷⁷Se-MNR data and Dr. Clifford E. Soll for providing MS data. NC thanks NYC LSAMP and National Science Foundation for the fellowships; DG thanks Pfizer for an undergraduate student summer fellowship. We also thank Drs. Alexander Greer, Paul Haberfield, and Richard Maliozzo for commenting on the manuscript.