BIOLOGICALLY-IMPORTANT FURANOSYL RINGS

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Several properties of biologically-important furanoses (i.e., solution composition and conformation, and kinetics of ring-opening and ring-closing reactions (tautomerization) will be studied. The experimental approach involves: A. Synthesis of structural variants of furanoses and furanose phosphates in all ring configurations to permit structure-function comparisons. Compounds will be labeled with stable isotopes (13C, 2H) to facilitate examination by high-field NMR spectroscopy. B. Identification and quantitation of the tautomeric forms present in aqueous solutions of furanoses by NMR, with particular attention given to carbonyl and hydrate forms. C. Measurement and conformational interpretation of three-bond 1H-1H, 13C-1H and 13C-13C coupling constants and spin-lattice (T1) relaxation times (13C, 1H) in furanosyl rings. Relaxation studies will involve the use of DESERT and dynamic NOE NMR methods to obtain absolute 1H-1H internuclear distances, from which conformation will be assessed. Preferred ring conformations deduced by NMR will be compared to those predicted by MO calculations. D. Measurement and interpretation of unidirectional rate constants of furanose tautomerization by NMR. Activation parameters will be measured for each component reaction. Solution studies of simple furanoses will be extended to the ribonucleosides and oligoribonucleotides. Several GC-rich oligoribonucleotides, having base sequences identical to those found in the stems of E. coli tRNAglu, will be prepared containing perdeutero-ribofuranosyl residues to facilitate NMR studies of their solution structures. The proposed studies are a prerequisite to the pursuit of the longer-term objective 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.