ORGN 699 |
| Zhen Huang, Nicolas Carrasco, and Quan Du. Department of Chemistry, Brooklyn College, and Programs of Biochemistry and Chemistry, The CUNY Graduate School and the University Center, 2900 Bedford Ave., Brooklyn, NY 11210 |
| We have developed a novel derivatization strategy via selenium replacement of nucleotide oxygen for phase determination, a limiting factor in nucleic acid X-ray crystallography. Unlike conventional halogen derivatization, selenium can be selectively introduced to many positions via oxygen replacement (e.g., 2'-, 3'-, 5'-ribose oxygen, furan ring oxygen, non-bridging phosphate oxygen, or oxygen on nucleobases). Position choice can avoid disruption of structure and function caused by modification. We have developed routes to synthesize Se-nucleoside phosphoramidites and triphosphates, Se-DNAs, and Se-RNAs. We have demonstrated for the first time nucleotide covalent derivatization with selenium in phase determination in nucleic acid X-ray crystallography. Se-77 stable isotope (7.6% natural abundance) is NMR-active, its spin number is ½, its natural signal is approximate three times more sensitive than C-13, and selenium can NMR-shift the nuclei around it. Therefore, this selenium labeling strategy can also be used in RNA structure determination with NMR. |
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Proteins, Peptides, Amino Acids, and Nucleotides
8:30 AM-11:30 AM, Thursday, September 11, 2003 Sheraton New York -- Royal Ballroom B, Oral
Division of Organic Chemistry |