Derivatization of DNAs with Selenium at 6-Position of Guanine for Function and Crystal Structure Studies
To investigate nucleic acid base pairing and stacking via atom-specific mutagenesis and crystallography, we have synthesized for the first time the 6-Se-deoxyguanosine phosphoramidite and incorporated it into DNAs via solid-phase synthesis with a coupling yield over 97%. We found that the UV absorption of the Se-DNAs red-shifts over 100 nm to 360 nm ({Epsilon} = 2.3 x 10{sup 4} M{sup -1} cm{sup -1}), the Se-DNAs are yellow colored, and this Se modification is relatively stable in water and at elevated temperature. Moreover, we successfully crystallized a ternary complex of the Se-G-DNA, RNA and RNase H. The crystal structure determination and analysis reveal that the overall structures of the native and Se-modified nucleic acid duplexes are very similar, the selenium atom participates in a Se-mediated hydrogen bond (Se H-N), and the {sup Se}G and C form a base pair similar to the natural G-C pair though the Se-modification causes the base-pair to shift (approximately 0.3 {angstrom}). Our biophysical and structural studies provide new insights into the nucleic acid flexibility, duplex recognition and stability. Furthermore, this novel selenium modification of nucleic acids can be used to investigate chemogenetics and structure of nucleic acids and their protein complexes.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 980134
- Report Number(s):
- BNL--93052-2010-JA
- Journal Information:
- Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 22 Vol. 36; ISSN 0305-1048; ISSN NARHAD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
36 MATERIALS SCIENCE
59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
ABSORPTION
ATOMS
BASES
COMPLEXES
COUPLING
CRYSTAL STRUCTURE
CRYSTALLOGRAPHY
DERIVATIZATION
FLEXIBILITY
FUNCTIONS
GUANINE
HYDROGEN
MODIFICATIONS
MUTAGENESIS
NUCLEIC ACIDS
PROTEINS
RNA
SELENIUM
STABILITY
SYNTHESIS
WATER
YIELDS
national synchrotron light source