Synthesis and characterization of oligodeoxyribonucleotides modified with 2′-thio-2′-deoxy-2′-S-(pyren-1-yl)methyluridine

Pyrene-functionalized oligonucleotides are intensively explored for applications in materials science and diagnostics. Here, we describe a short synthetic route to 2′-S-(pyren-1-yl)methyl-2′-thiouridine monomer S, its incorporation into oligodeoxyribonucleotides (ONs), and biophysical characterization thereof. Pseudorotational analysis reveals that the furanose ring of this monomer has a slight preference for South-type conformations. ONs modified with monomer S display high cDNA affinity but decreased binding specificity. Hybridization is associated with bathochromic shifts of pyrene absorption bands and quenching of pyrene fluorescence consistent with an intercalative binding mode of the pyrene moiety. Monomer S was also evaluated as a building block for mixed-sequence recognition of double-stranded DNA via the Invader strategy. However, probes with +1 interstrand arrangements of monomer S were found to be less efficient than Invader probes based on 2′-O-(pyren-1-yl)methyluridine or 2′-N-(pyren-1-yl)methyl-2′-N-methyl-2′-aminouridine.

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