Triazole‐Linked Oligonucleotides with Mixed‐Base Sequences: Synthesis and Hybridization Properties

Abstract

AbstractA new class of backbone‐modified oligonucleotide analogs has emerged since the discovery of the CuI‐catalyzed [3+2] azide/alkyne cycloaddition reaction. These are oligonucleotide analogs with 1,4‐disubstituted 1,2,3‐triazoles as the internucleotide linkages. Of all such analogs known, only the triazole‐linked deoxythymidine decamer [(dT)10] has been reported to show enhanced binding affinity to complementary DNA. Importantly, it is a fully modified (dT)10 analog. To date, sequentially heterogeneous oligonucleotides bearing the same backbone modification have not been described. With the goal of investigating sequence and regularity dependence of the effect of this modification on duplex stability, we have designed partially modified mixed‐base oligonucleotides, which can be prepared by using a modified dinucleoside block. In this paper we report the synthesis of a dithymidine phosphoramidite analog with a triazole linker, its use in oligonucleotide synthesis and hybridization data of the resulting oligonucleotide analogs. The effect of single and multiple modifications on stability of mixed‐base duplexes is assessed and compared with published data for the oligo(T)/oligo(A) duplex. We also compared the effect of the linker concerned with that of a shorter triazole linker.