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Triazole‐Linked Oligonucleotides with Mixed‐Base Sequences: Synthesis and Hybridization Properties
Author(s) -
Varizhuk Anna,
Chizhov Alexandr,
Smirnov Igor,
Kaluzhny Dmitry,
Florentiev Vladimir
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201101700
Subject(s) - oligonucleotide , linker , phosphoramidite , chemistry , combinatorial chemistry , duplex (building) , click chemistry , triazole , stereochemistry , oligonucleotide synthesis , base pair , azide , dna , biochemistry , organic chemistry , computer science , operating system
Abstract A new class of backbone‐modified oligonucleotide analogs has emerged since the discovery of the Cu I ‐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.