2′-aminoethoxy-2-amino-3-methylpyridine in triplex-forming oligonucleotides: High affinity, selectivity and resistance to enzymatic degradation

Abstract

The phosphoramidite monomer of the C-nucleoside 2′-aminoethoxy-2- amino-3-methylpyridine (AE-MAP) has been synthesized for the first time and incorporated into triplex-forming oligonucleotides (TFOs). Ultraviolet melting and DNase I footprinting studies show that AE-MAP is a potent triplex-stabilizing monomer that is selective for GC base pairs. TFOs containing AE-MAP bind with high affinity to duplexes but only weakly to single stranded DNA. In addition, AE-MAP confers high nuclease resistance on oligonucleotides. TFOs containing AE-MAP have potential for gene knock-out and gene expression studies. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.