Design and Synthesis of Triazolyl‐Donor/Acceptor Unnatural Nucleosides and Oligonucleotide Probes Containing Triazolyl‐Phenanthrene Nucleoside

Abstract

In the context of abasic DNA or DNA duplex stabilization, several unnatural nucleosidic/non‐nucleosidic base surrogates have been reported. Toward this end, we have designed and synthesized triazolyl‐aromatic donor chomophores as unnatural nucleoside analogs. These modifications display markedly higher thermal stabilization of abasic DNA duplex in comparison to the stabilization offered by other nucleoside/non‐nucleoside base surrogates reported in the literature. The same oligonucleotide probe containing triazolylphenanthrene nucleotide also offers very good stability of the self‐pair duplex via π‐π stacking interaction and hetero‐pair duplex via charge transfer interaction when paired against triazolyl acceptor aromatic nucleoside. Moreover, the probe in the reverse sequence containing triazolylphenanthrene nucleotide has shown FRET efficiency in a chimeric DNA duplex. The triazolyl nucleotides would expectedly show stability toward exonuclease activity. This unit describes protocols for chemical synthesis of unnatural triazolyl nucleosides and one oligonucleotide probe. The unit also provides a summary of various thermal and photophysical applications of triazolylphenantherene‐containing oligonucleotides. Curr. Protoc. Nucleic Acid Chem. 58:1.32.1‐1.32.27. © 2014 by John Wiley & Sons, Inc.