The conformations of two phosphodiester‐linked dinucleotides and their analogues containing a 3′‐S‐phosphorothiolate linkage were investigated using 1H NMR spectroscopy. The phosphorus decoupled 1H NMR spectrum of each compound was simulated and values for the vicinal proton–proton coupling constants of the sugar ring hydrogens abstracted at several different temperatures, for use in full conformational analyses. The UV absorbance temperature profiles of the dimers were also analysed. It was found that in both the deoxyribo and ribo analogues the sugar ring conformations are affected by the phosphorothiolate modification, with a large increase in the percentage of north‐type puckering. This change is mainly due to the decrease in the influence of the gauche effect between the 3′‐substituent and the O4′‐ring oxygen experienced when substituting an oxygen atom for the less electronegative sulphur atom. Copyright © 1999 John Wiley & Sons, Ltd.

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The conformations of two phosphodiester-linked dinucleotides and their analogues containing a 3 0 -S-phosphorothiolate linkage were investigated using 1 H NMR spectroscopy. The phosphorus decoupled 1 H NMR spectrum of each compound was simulated and values for the vicinal proton-proton coupling constants of the sugar ring hydrogens abstracted at several different temperatures, for use in full conformational analyses. The UV absorbance temperature profiles of the dimers were also analysed. It was found that in both the deoxyribo and ribo analogues the sugar ring conformations are affected by the phosphorothiolate modification, with a large increase in the percentage of north-type puckering. This change is mainly due to the decrease in the influence of the gauche effect between the 3 0 -substituent and the O4 0 -ring oxygen experienced when substituting an oxygen atom for the less electronegative sulphur atom.

Two dinucleoside monophosphate analogues containing disulfide linkages (1 and 2) have been prepared for incorporation into oligonucleotides. The modified oligomers will be tested for their potential as antisense agents.INTRODUCTION Synthetic oligonucleotides with favourable antisense properties are few in number. Whilst many nuclease-resistant analogues have been prepared, relatively few of these have displayed favourable hybridization properties with their target RNA. Recently, backbone modifications which confer structural rigidity have attracted interest as they may provide the necessary preorganization requirements for optimal duplex formation. Solution conformation studies have shown that disulfide bonds exist as rigid systems which are conformationally restricted.1 Thus oligonucleotides in which the phosphodiester bonds are replaced with neutral, achiral disulfide linkages (1 and 2) are attractive antisense candidates since they are not only expected to be nuclease resistant but they may also display good hybridization properties.

Dinucleoside Monophosphate Analogues Containing Disulfide Linkages.-The synthesis of two novel dinucleosides with modified internucleosidic linkages [cf. (VIII), (XVII)], attractive antisense candidates, for incorporation into oligonucleotides is described.-(WITCH, E. M.; COSSTICK, R.; Nucleosides Nucleotides 16 (1997) 7-9, 1555-1558 Robert Robinson Lab., Dep. Chem., Univ. Liverpool, Liverpool L69 3BX, UK; EN)