2'-SEME-MODIFIED OLIGONUCLEOTIDES

Brookhaven Science Assoc-Brookhaven Lab, Upton NY

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In this work, we would like to further prove that selenium derivatization can greatly facilitate the phase determination and help to resolve the structures of macromolecules. Since the selenium strategy have greatly facilitated the structure determination in the field of protein, it can also be used in nucleic acid field, which actually has been proved by our lab. Besides the phase determination,we also found that selenium modification at the 2'position can make the crystals grow much faster in some sequences(less than one hour~!)than native ones. Here is an example, we got the crystals for this selenium contained nucleic acid sequence (5'-GU(2'-Se)GTACAC-3') in a short time. So, in addition to check the phase determination to widen it's application, we also like to know more structural details from the X-ray crystallography, such as hydration pattern and sugar packing, etc. It will be helpful to solve the cryallization and phase problem, the two main difficulties in the field of nucleic acid structure study.