Synthesis and hybridization data of oligonucleotide analogs with triazole internucleotide linkages, potential antiviral and antitumor agents

Triazolyl-functionalized oligonucleotide (ON) analogs have received much attention as potential antitumor and antiviral agents. The most promising of such analogs are those exhibiting high binding affinity toward native DNA/RNA, since they may prove to be efficient antisense or siRNA agents. To date, relatively few ON analogs with triazole internucleotide linkages have been described. In this paper, we report an improved synthesis of a modified dinucleoside phosphoramidite and hybridization data of ON analogs with four-bond triazole internucleotide linkages. We believe these data are essential for comprehensive analysis of the relation between the length of triazole internucleotide linkages and duplex stability.

Graphical abstractTriazolyl-modified oligonucleotides were synthesized and their hybridization with complementary DNA was studied.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Improved synthesis of a triazolyl-modified dinucleoside block is described. ► The block is used to obtain oligonucleotide analogs, potential therapeutic agents. ► The analogs have decreased binding affinity to complementary DNA. ► Four-bond triazole linkers disrupt duplex structure. ► Six-bond backbone periodicity is essential for duplex stability.