Selective binding of looped oligonucleotides to a single-stranded DNA and its influence on replication in vitro.

Complexing of looped and circular oligonucleotides, composed of either 2'-deoxyribo- or 2'-O-methylribonucleoside units, with completely matching or partially mismatching complementary DNA sequences was studied. Melting experiments revealed considerable differences among the stabilities of these hybrid complexes. Maximum stability and selectivity was displayed by oligomers 2 and 5. It was concluded that a linear stretch, attached to 1'-O- of 3'-deoxypsicothymidine unit (Z) increases the selectivity of hybridisation and stability of the complex as a whole. This allows one to aim the target DNA very precisely at its polyadenine part as well as at adjacent sequence simultaneously. Experiments on termination of primer extension catalysed by different DNA-polymerases--Sequenase, Klenow fragment and Tth--have demonstrated that looped oligomer 5, composed of 2'-O-methylribonucleosides appears to be a highly selective and potent inhibitor of replication in vitro. Features of looped oligonucleotides, composed of 2'-O-methylribonucleosides seem to be useful for design of highly specific antigene oligonucleotides

Looped oligonucleotides form stable hybrid complexes with a single-stranded DNA.

Several new branched (1, 2), circular (9) and looped oligonucleotides (14-17) were synthesized. 3'-Deoxypsicothymidine was employed to create the site of branching when required. The circular and looped structures were obtained by oxidative disulfide bond formation between mercaptoalkyl tether groups. All the oligonucleotides prepared contained two T11 sequences, and the branched and looped oligomers an additional alternating CT sequence. The melting experiments revealed that the branched oligonucleotides form relatively weak hybrid (double/triple helix) complexes with the single-stranded oligodeoxyribonucleotide, showing a considerable destabilizing effect produced by the structure at the point of branching. The data obtained with looped oligonucleotides demonstrated considerable stabilization of the hybrid (double/triple helix) complexes with the complement. The data reported may be useful in attempting to design new antisense or antigene oligonucleotides capable of forming selective and stable bimolecular hybrid complexes with nucleic acids

Hydrolytic stability of potential antiviral nucleoside analogues: 3'-substituted 2',3'-dideoxy- and 2',3'-didehydro-2',3'-dideoxyribonucleosides

status: publishe

Solution conformation and hydrolytic stability of 2 '-substituted and 3'-substituted 2',3'-dideoxyribonucleosides, including some potential inhibitors of human immunodeficiency virus

Sugar ring conformations of a number of 2'- and 3'-substituted 2',3'-dieoxyribonudeosides were determined in (H2O)-H-2 by H-1 NMR spectroscopy. First-order rate constants for the cleavage of their N-glycosidic bond in aqueous acid were measured. The dependence of sugar ring conformation and hydrolytic stability on the polar nature of the 2'/3'-substitutent is discussed.status: publishe

Synthesis, solution conformations and hydrolytic stability of 3'-substituted 2'-deoxyribonucleosides

status: publishe

Synthesis of acylamino acid esters of nucleoside 5'-phosphates and their investigation with PMR and CD spectra.

The acylamino acid esters of nucleoside 5'-phosphates are synthesized via condensation of N-(N'-acylaminoacyl) imidazoles with nucleoside 5'-phosphates. The PMR and CD spectra of the esters obtained are studied. The 3'-isomers of the substances under study are observed to have a shift in the conformational N in equilibrium S equilibrium of the carbohydrate moiety in favour of the S-form as compared to the initial nucleosides and their 2'-acyl esters