Active derivatives of oligonucleotides with a zwitterionic terminal phosphate group for design of affinity reagents and probes

Method of synthesis and isolation of oligonucleotide derivatives with a zwitterionic terminal phosphate group, containing N-methylimidazole (MeIm), 4-dimethylaminopyridine (DMAP) or 4-dimethylaminopyridine 1-oxide (DMAPO) residues has been developed. Mononucleotide derivatives were used to study the reactivity of these compounds to various nucleophiles and the dependence of hydrolysis rate on pH of solution. These compounds interact rapidly and quantitatively with aliphatic amines and much slower with water, aniline and methanol. MeIm derivatives are most active to nucleophiles, whereas the reactivity of DMAP derivatives is ca. 5 times lower and that of DMAPO derivatives is lower by 2 order of magnitude. This method of activating terminal phosphate group is promising for synthesis of various oligonucleotide phosphoramidates.