Stability of a 2′‐O‐(Carbamoylmethyl)adenosine‐Containing Dinucleotide

Abstract

AbstractIn the interest of pursuing the synthesis of 2′‐O‐carbamoylmethyl‐modified oligonucleotides from building blocks already containing the modification, we have performed studies on the chemical and enzymatic stability of a 2′‐O‐carbamoylmethyl‐modified dinucleotide. The dinucleotide was subjected to ammonolysis and other basic conditions such as treatment with ethylenediamine and sodium hydroxide at different temperatures. The amide of the carbamoylmethyl group partially hydrolyzed under standard deprotection conditions for oligonucleotide synthesis (conc. aq. NH3 at 55 °C). However, under several other conditions, including saturated NH3 in methanol, the amide remained intact. Treatment of the dinucleotide with Phosphodiesterase I from Crotalus adamanteus venom and Phosphodiesterase II from Bovine spleen, showed that the carbamoylmethyl moiety gives substantial protection of the phosphodiester towards enzymatic degradation.