Abstract

The purpose of this project is to determine the effects of light on model nucleic acids, and how alterations in chemical structure and conformation relate to modified biological activities (mutagenesis and carcinogenesis). Ribosyl- and deoxy- oligonucleotides of defined sequence are chemically synthesized. These nucleic acids contain normal and fluorinated bases. They are irradiated with different wavelengths of light, but concentrating on the ultraviolet-B region (280-320 nm). Various photosensitizers are used in the presence and absence of oxygen. The photoproducts which result are separated and purified in the intact nucleic acid using TLC and HPLC, and are structurally characterized using UV, mass spectrometry and NMR. The conformation of the various photoproducts are determined as well as the effects they transmit to neighboring regions of the normal nucleic acid using multi- nuclear magnetic resonance spectroscopy, x-ray crystallography, molecular modelling and energy minimization techniques.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039027-08
Application #
3177667
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1984-12-01
Project End
1993-11-30
Budget Start
1991-12-01
Budget End
1993-11-30
Support Year
8
Fiscal Year
1992
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