Abstract

The purpose of this project is to determine the effects of light on the structure and conformation of model nucleic acids, and how alterations in structure and conformation relate to modified biological activities (mutagenesis and carcinogenesis). Oligonucleotides of defined base sequence will be synthesized. The oligomers will be irradiated with 254 nm or 310 nm light. The oligomer-photoproducts will be separated and purified by TLC and HPLC, and characterized by UV, NMR, and mass spectroscopy. The conformation of normal ribosyl- and deoxyribosyl-oligomers will be compared to their photoproduct-counterparts by multi-nuclear magnetic resonance spectroscopy, x-ray crystallography whenever possible, and computer graphic model building techniques.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA039027-01
Application #
3177658
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263

  Publications

Tabaczynski, W A; Lemaire, D G; Ruzsicska, B P et al. (1999) An NMR and conformational investigation of the trans-syn cyclobutane photodimers of dUpdT. Biopolymers 50:185-91
Pechenaya, V I; Danilov, V I; Slyusarchuk, O N et al. (1995) Theoretical investigation of excimer and exciplex states of uracil and halogen derivatives: effect of nonparallelism of bases. Photochem Photobiol 61:435-41
Kim, J K; Soni, S D; Arakali, A V et al. (1995) Solution structure of a nucleic acid photoproduct of deoxyfluorouridylyl-(3'-5')-thymidine monophosphate (d-FpT) determined by NMR and restrained molecular dynamics: structural comparison of two sequence isomer photoadducts (d-U5p5T and d-T5p5U). Nucleic Acids Res 23:1810-5
Alderfer, J L; Soni, S D; Arakali, A V et al. (1993) UV irradiation of nucleic acids: characterization of photoproducts of thymidylyl-(3'-->5')-2'-deoxy-5-fluorouridine. Photochem Photobiol 57:770-6
Blazek, E R; Alderfer, J L; Tabaczynski, W A et al. (1993) A 5-4 pyrimidine-pyrimidone photoproduct produced from mixtures of thymine and 4-thiouridine irradiated with 334 nm light. Photochem Photobiol 57:255-65
Tabaczynski, W A; Lemaire, D G; Ruzsicska, B P et al. (1993) An NMR and conformational investigation of the trans-syn cyclobutane photodimers of dTpdU. Biopolymers 33:1365-75
Kim, J K; Soni, S D; Wallace, J C et al. (1993) Solution structure of nucleic acid photoadduct, deoxy-m5HO6-uridylyl(5-5)(3'-5')deoxyuridine by NMR and restrained molecular dynamics. Nucleic Acids Res 21:2755-9
Kim, J K; Wallace, J C; Alderfer, J L (1993) Substituent effects on the puckering mode of the cyclobutane ring and the glycosyl bond of cis-syn photodimers. Biopolymers 33:713-21
Danilov, V I; Slyusarchuk, O N; Poltev, V I et al. (1992) A Monte Carlo simulation of hydration of xanthine-derivatives and their stacked forms. J Biomol Struct Dyn 9:1239-52
Kim, J K; Alderfer, J L (1992) Conformational variations of the cis-syn cyclobutane-type photodimer in DNA and RNA. J Biomol Struct Dyn 9:705-18

Showing the most recent 10 out of 15 publications