This proposal addressed several fundamental problems in the chemistry and biochemistry of biologically-important furanose and furanose-containing compounds. The experimental approach involves the combination of stable isotopic enrichment, modern multi-pulse 1D and 2D NMR spectroscopy, and computational chemistry (ab initio molecular orbital calculations). New/improved methods (chemical and enzymic) will be developed to introduce stable isotopes (13C,2H) into carbohydrates, with particular focus on furanose sugars. By preparing systematically a variety of furanose structures, we aim to: A) Study the tautomeric composition of these (13C)-enriched furanose rings in aqueous solution as a function of ring structure/configuration. B) Study the conformational/dynamic properties of these (13C)- enriched furanoses as a function of ring structure and configuration. This will be accomplished by interpreting long- range 1H-1H, 13C-1H and 13C-13C coupling constants obtained from high-resolution NMR spectra. Theoretical input to these studies will be supplied by molecular orbital calculations (geometry optimization). C) Study how furanose ring structure/configuration, and other factors, affect the rates of ring-opening and ring-closing reactions in solution (furanose anomerization). For example, the effect of ring alkylation on these rates (Thorpe-Ingold effects) will be examined. D) Study how furanose ring conformation/dynamics are altered when incorporated into oligonucleotides; specific-sequence oligonucleotides containing stable isotopes will be used in this work. The proposed studies are a prerequisite to the pursuit of the longer-term objectives of determining the molecular basis for the binding specificity between nucleic acids and proteins, and on elucidating the effect of sugar tautomerization on metabolic regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033791-05
Application #
3283831
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1984-12-01
Project End
1991-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Notre Dame
Department
Type
Schools of Arts and Sciences
DUNS #
824910376
City
Notre Dame
State
IN
Country
United States
Zip Code
46556
Wu, J; Serianni, A S (1994) 13C-labeled oligodeoxyribonucleotides: a solution study of a CCAAT-containing sequence at the nuclear factor I recognition site of human adenovirus. Biopolymers 34:1175-86
Podlasek, C A; Serianni, A S (1994) 19F and 13C NMR studies of polyol metabolism in freeze-tolerant pupae of Hyalophora cecropia. J Biol Chem 269:2521-8
Duker, J M; Serianni, A S (1993) (13C)-substituted sucrose: 13C-1H and 13C-13C spin coupling constants to assess furanose ring and glycosidic bond conformations in aqueous solution. Carbohydr Res 249:281-303
Wu, J; Serianni, A S; Bondo, P B (1992) Multiply 13C-substituted monosaccharides: synthesis of D-(1,5,6-13C3)glucose and D-(2,5,6-13C3)glucose. Carbohydr Res 226:261-9
Wu, J; Serianni, A S (1992) Isotope-edited 1D and 2D n.m.r. spectroscopy of 13C-substituted carbohydrates. Carbohydr Res 226:209-18
Wu, J A; Serianni, A S (1991) D-Penturonic acids: solution studies of stable-isotopically enriched compounds by 1H- and 13C-n.m.r. spectroscopy. Carbohydr Res 210:51-70
Snyder, J R; Serianni, A S (1991) Deoxygenated and alkylated furanoses: Thorpe-Ingold effects on tautomeric equilibria and rates of anomerization. Carbohydr Res 210:21-38
Vuorinen, T; Serianni, A S (1991) Synthesis of D-erythro-2-pentulose and D-threo-2-pentulose and analysis of the 13C- and 1H-n.m.r. spectra of the 1-13C- and 2-13C-substituted sugars. Carbohydr Res 209:13-31
Wu, J; Serianni, A S (1991) Ring-opening kinetics of the D-pentofuranuronic acids. Carbohydr Res 211:207-17
Vuorinen, T; Serianni, A S (1990) 13C-substituted pentos-2-uloses: synthesis and analysis by 1H- and 13C-n.m.r. spectroscopy. Carbohydr Res 207:185-210

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