Oxygen Replacement with Selenium at the Thymidine 4-Position for the Se Base Pairing and Crystal Structure Studies
The T-A and C-G base pairing and stacking allow the formation of the stable DNA duplex structure for genetic information storage, transcription, and replication. To replace the oxygen of the nucleotide nucleobases with selenium for the studies of the base-pair recognition, the duplex stability, and the nuclei acid crystal structures, we have synthesized for the first time the 4-Se thymidine phosphoramidite and incorporated it into oligonucleotides via solid-phase synthesis with high coupling yield (99%). The Se modification on the nucleobase is relatively stable under the elevated temperature. Using the dU{sub Se} (2'-Se-dU) to facilitate the crystallization, we have successfully crystallized the DNA containing the 4-Se-T substitution and determined its structure at 1.50 {angstrom} resolution. The UV-melting and X-ray crystal structure studies have indicated that the Se substitution on the nucleobase does not cause a significant structure perturbation, the large Se atom on the thymine can be successfully accommodated by the DNA duplex, and the Se-mediated hydrogen bond (longer than the usual hydrogen bond) is formed within the modified T-A base pair. In addition, the Se derivatization on the nucleobases further facilitates X-ray crystal structure determination of nucleic acids and their protein complexes via Se MAD phasing.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 930360
- Report Number(s):
- BNL--81079-2008-JA
- Journal Information:
- Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Vol. 129; ISSN JACSAT; ISSN 0002-7863
- Country of Publication:
- United States
- Language:
- English
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