Optimized DNA targeting using N,N-bis(2-pyridylmethyl)-β-alanyl 2′-amino-LNA

Abstract

Incorporation of N,N-bis(2-pyridylmethyl)-β-alanyl 2′-amino-LNA (bipyridyl-functionalized 2′-amino locked nucleic acid) monomers into DNA strands enables high-affinity targeting of complementary DNA with excellent Watson–Crick selectivity in the presence of divalent metal ions. Positioning of bipyridyl-functionalized 2′-amino-LNA monomers in two complementary DNA strands in a “3′-end zipper” constitution allows modulation of duplex stability, i.e., a strong stabilizing effect with one equivalent of divalent metal ion per bipyridyl pair, or a strong destabilizing effect with an excess of divalent metal ions.