Base stacking is the single most important factor in determing DNA structure and stability. Interactions arising from pi stacking forces also result in DNA intercalationof anthracycline antitumor agents and metabolites of carcinogenic hydrocarbons. Intercalation gives rise to the pooling of these ligands in DNA which is a major biological target site. Intercalation is also necessary for DNA stabilizatoin which accompanies anthracycline binding and which is an essential component of anthracycline antitumor activity. For hydrocarbon metabolites pi binding to DNA is of the same magnitude as hydrogen bonding forces which are responsible for the storage and transmission of genetic information. It is likely that the biological activity of hydrocarbon metabolites depends significantly on the ability of these molecules to participate in such reversible binding interactions when they are covalently incorporated into DNA. Several examples exist where decreases in pi ionization potentials accompany increases in pi stacking forces which occur naturally in DNA and RNA and which lead to intercalation. In the proposed study this relatioship will be explored further. An inverse correlation between ionization potential and complex stability occurs when binding arises from induced dipole-induced dipole interactions that increase with the increasing polarizabilities of the interacting partners. In these complexes reversible binding forces play a crucial biochemical role but are generally weak (approximately 10 kcal/mole). It is difficult to obtain accurate values of molecular polarizabilities upon which binding depends. It is much easier, using UV photoelectron techniques and results from molecular orbital calculations, to obtain valence orbital ionization protentials. In this investigation UV photoelectron spectroscopy and molecular orbital calculation will be employed to understand how valence eletronic structure influences reversible binding interactions involving nucleotides, anthracycline antitumor agents and carcinogenic hydrocarbon metabolites.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041432-03
Application #
3181900
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1987-05-01
Project End
1991-04-30
Budget Start
1989-05-01
Budget End
1991-04-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612