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The triplex-forming abilities of some conformationally restricted nucleotide analogs are disclosed and compared herein. 2′-Amino-LNA monomers proved to be less stabilising to triplexes than LNA monomers when incorporated into a triplex-forming third strand. N2′-functionalisation of 2′-amino-LNA monomers with a glycyl unit induced the formation of exceptionally stable triplexes. Nucleotide analogs containing a C2′,C3′-oxymethylene linker (E-type furanose conformation) or a C2′,C4′-propylene linker (N-type furanose conformation) had no significant effect on triplex stability proving that conformational restriction per se is insufficient to stabilise triplexes.

Graphical abstract: LNA (locked nucleic acid) and analogs as triplex-forming oligonucleotides

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