We wish to elucidate the detailed conformations of DNA in solution, and to investigate their relationships to genetic function, interactions with drugs, and protein recognition. The method we have chosen to carry out such studies in solution is nuclear magnetic resonance (NMR) spectroscopy. We have tested the factors which contribute to the B to Z conformational transition in polydeoxynucleotides, and we have studied the solution conformation of the homopolymer poly(dA) poly(dT) about which there has been controversy in the literature. The specific method used to detail these solution conformations is the 2D-NOE NMR method, which provides relative interatomic distances. Loops in DNA are expected to be important for protein recognition of selective genetic sites, such as RNA polymerase promotor sequences. Consequently, we have studied quasipalindromic synthetic oligonucleotides, and have delineated the mechanism of hairpin loop formation. In order to specify the mobility of different portions of the DNA molecule, particularly the deoxyribose ring, we have carried out novel syntheses of selectively deuterated nucleosides. This allows us to use solid state deuterium NMR, which is the least ambiguous NMR method available to determine local molecular mobility.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Treatment (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CM006521-02
Application #
3939543
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Cancer Treatment
Department
Type
DUNS #
City
State
Country
United States
Zip Code