Oxygen Replacement with Selenium at the Thymidine 4-Position for the Se Base Pairing and Crystal Structure Studies

摘要

We have synthesized the 4-Se thymidine phosphor-amidite (4) and incorporated it into oligonucleotides with quantitative yield. The Se substitution on the nucleobase is relatively stable under the elevated temperature. By the UV-melting and crystal structure studies, we have further demonstrated that the O substitution with Se on the nucleobase does not cause the significant duplex structure perturbation. The crystal structure study also reveals the accommodation of the large Se atom on the thymine by the DNA duplex and the formation of the Se-mediated hydrogen bond within the T-A base pair. This work will stimulate the studies on the Se substitution on other nucleobases and positions, opening a new avenue for further exploring the base-paring selectivity governed by the hydrogen bond and base shape, the duplex structure and flexibility, the DNA replication efficiency and fidelity, and the poly-merase recognition of the modified nucleobases. Moreover, the Se derivatization on the nucleobases will largely facilitate X-ray crystal structure studies of nucleic acids as well as their protein complexes.