Anna Trifonova

THE SYNTHESIS OF DEUTERIONUCLEOSIDES

Abstract The synthesis of deuterionucleosides for site-specific incorporation into oligo-DNA or -RNA is herein reviewed for NMR or biological studies. The review covers the following aspects: (i) deuteration of the aglycone; (ii) single-site chemical deuteration of the sugar residues; (iii) multiple-site chemical deuteration of the sugar residues; (iv) enzymatic synthesis of deuterated nucleosides or nucleotides; and (v) synthesis of labelled nucleosides with multiple isotopes.

SYNTHETIC STUDIES TO IMPROVE THE DEUTERIUM LABELLING IN NUCLEOSIDES FOR FACILITATING STRUCTURAL STUDIES OF LARGE RNAS BY HIGH-FIELD NMR SPECTROSCOPY

Synthetic studies to prepare ribonucleosides deuterated at C2′ and the application of the developed procedures for the synthesis of 2 H 5 -ribonucleosides from 1,2-O-isopropylidene-3-O-benzyl-ribofuranose-3,4,5,5′- 2 H 4 have been reported.

Diastereospecific chemical synthesis of ribonucleosides-3′,4′,5′,5″ -d4

Abstract The diastereospecific chemical syntheses of uridine-3′,4′,5′,5″ -d4, cytidine-3′,4′,5′,5″ -d4, adenosine-3′,4′,5′,5″ -d4 and guanosine-3′,4′,5′,5″ -d4 (>97 atom % 2H at C3′, C4′ and C5′) have been achieved by condensation of appropriately protected aglycone with 1-O-acetyl 2,3,5- tri -O-(4- toluoyl )- α β - D -ribofuranose-3,4,5,5′ -d 4 (27), which has been obtained in an overall yield of 20 % in 11 steps starting from 50 mmol of 2:5,6- Di -O- isopropylidene -α- D -glucose .

Selective cleavage of the O6-diphenylcarbamoyl group from sugar-modified guanosines for incorporation into oligo-RNA

Abstract A facile conversion of 2′,3′,5′- O -tri-(Bz, Tol or Ac)- N 2 -(Ac or iBu)- O 6 -DPC-guanosine to N 2 -(Ac or iBu)-guanosine has been achieved in 89–98% yield by short treatment with 90% aqueous TFA for smooth cleavage of the DPC group followed by treatment with sodium ethoxide in pyridine-ethanol mixture at room temperature.

DO THE 16 MER, 5′-GUGGUCUGAUGAGGCC-3′ AND THE 25 MER, 5′-GGCCGAAACUCGUAAGAGUCACCAC-3′, FORM A HAMMERHEAD RIBOZYME STRUCTURE IN PHYSIOLOGICAL CONDITIONS? AN NMR AND UV THERMODYNAMIC STUDY

In a wide range of salt concentrations, 10–30 mM phosphate buffer containing up to 0.5 M Li2SO4 and 300 mM NaCl, 7.5 mM Mg2+, pH 5.5–7.5, a mixture of the 16 mer and the 25 mer RNA strands does not form a hammerhead in any amount detectable by NMR at 600 MHz. The imino-, amino-, aromatic- and anomeric protons in the NMR spectra of both the 16 mer and the 25 mer RNA have been assigned separately. Both the 16 mer and the 25 mer RNA both take up very stable hairpin structures, and when mixed together there is no major change of conformation in neither oligo-RNA.