[Chemical reactions in double-stranded nucleic acids. VI. N-hydroxybenzotriazole esters of oligonucleotides--reagents for synthesis of DNA-duplexes with modified sugar-phosphate backbone].

With the aid of a new type of phosphorylating agents, N-hydroxybenzotriazole phosphodiesters of oligonucleotides, template-directed synthesis of DNA duplexes was carried out with ribonucleotide, aliphatic diamine or amino acid residues at a predetermined position of the sugar-phosphate backbone. Introduction of a ribonucleotide into an oligonucleotide strand gives rise to a mixture of 2'-5' and 3'-5' isomers, whose ratio depends on the condensation conditions. Residues of amino acids (lysine, serine, tyrosine) or aliphatic diamines were substituted for one or two mononucleotides in the duplex. Phosphoamide bonds with the participation of an aliphatic diamine or lysine are formed most efficiently in the presence of N-methylimidazole and if the reacting groups are in the close proximity to each other. Phosphodiester bond synthesis with the participation of hydroxy groups of serine or tyrosine proceeds less effectively. Oligonucleotide N-hydroxybenzotriazole esters exceeds previously used phosphoimidazolides in efficiency of the chemical ligation. An amino acid residue incorporated into the duplex may be used in construction of new compounds by joining the carboxyl with various groups.