Zwitterionic oligonucleotides: A study on binding properties of 2′-O-aminohexyl modifications

2′-O-Aminohexyl side chains provide excellent conditions for zwitterionic interstrand and intrastrand interactions of oligonucleotides. 2′-O-Aminoalkylated phosphoramidites of adenosine and undine were synthesized and incorporated in increasing number into homo adenosine and homo uridine/thymidine dodecamers, respectively. CD spectra of these dodecamers with complementary sense DNA exhibited a B-DNA type structure. While duplex stability values of all tested oligonucleotides were lower than those of the native oligonucleotides, they were significantly higher than those of 2′-O-heptyl modified oligonucteotides. The destabilization amounted to 0.9, 1.5, and 2.7°C per modification for 2′-O-aminohexyl adenosine, 2′-O-aminohexyl undine, and 2′-O-heptyl adenosine substitutions. These findings are pointing to a duplex stabilizing effect of the interaction of side chain amino groups with backbone phosphoric acid.