Dinucleoside Monophosphate Analogues Containing Disulfide Linkages

Abstract

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.

Synthesis, Dynamic Combinatorial Chemistry, and PCR Amplification of 3′–5′ and 3′–6′ Disulfide‐linked Oligonucleotides

“…Disulfides are known to exist in dynamic exchange equilibria in the presence of thiolate, a process known to alter the structure of proteins,2 and are commonly exploited within the field of dynamic combinatorial chemistry to generate novel ligands and receptors 3–7. Disulfide‐linked dinucleosides have previously been synthesized by Witch et al 8. Only recently was the disulfide linkage incorporated into oligonucleotides as an internucleosidic linkage 9.…”

Synthesis, Dynamic Combinatorial Chemistry, and PCR Amplification of 3′–5′ and 3′–6′ Disulfide‐linked Oligonucleotides

“…[1] Disulfides are known to exist in dynamic exchange equilibria in the presence of thiolate, a process known to alter the structure of proteins, [2] and are commonly exploited within the field of dynamic combinatorial chemistry to generate novel ligands and receptors. [3][4][5][6][7] Disulfide-linked dinucleosides have previously been synthesized by Witch et al [8] Only recently was the disulfide linkage incorporated into oligonucleotides as an internucleosidic linkage. [9] Patzke et al utilized a DNA-templated reaction between an activated disulfide and a thiol to generate a fast ligation reaction.…”