Within the realm of chemistry the specific aims of this project are: 1) to develop new methodology for incorporating fluorine atoms into the carbohydrate moiety of nucleosides; 2) to devise synthetic routes to nucleotide analogs in which 0-3' or 0-5' are replaced by the CF2 group; 3) to synthesize analogs of nucleoside polyphosphates and oligonucleotides in which the anionic P-O- group is replaced by the P-CF3 group. The primary area of exploration with regard to fluoronucleosides will be a search for methods to incorporate a CF2 unit at C-2' of ribose in place of the CHOH group. Both direct modification at the nucleoside level as well as de novo fluorosugar syntheses will be pursued. Structural studies are planned to ascertain the influence of the CF2 and CF3 groups on nucleoside and nucleotide structure, from which increased understanding about the factors that contribute to the sugar-phosphate backbone conformation of polynucleotides may be gained. One objective of our research program is to create nucleoside analogs and molecular probes for studying the biochemistry of DNA replication. Where appropriate, the effect of some of these analogs (nucleoside 5'-triphosphates modified on either C-2', C-5', or phosphorous) on DNA synthesis will be examined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI020480-01A1
Application #
3130169
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1985-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of North Dakota
Department
Type
Schools of Arts and Sciences
DUNS #
102280781
City
Grand Forks
State
ND
Country
United States
Zip Code
58202
Bergstrom, D E; Mott, A W; De Clercq, E et al. (1992) 3',3'-Difluoro-3'-deoxythymidine: comparison of anti-HIV activity to 3'-fluoro-3'-deoxythymidine. J Med Chem 35:3369-72