[Modification of nucleic acids by reactive oligonucleotide derivatives having a 5'-terminal nitrogen yperite residue, covalently bound with linkers of varying length. Conformation dynamics of group reactivity in complementary complexes].

By optimizing the length of a linker bearing 5'-terminal alkylating 4-[methyl-(2-chloroethyl)amino]benzylphosphoramide residue, a reactive oligodeoxyribonucleotide derivative has been constructed with an optimal ability to alkylate nucleic bases in a double-stranded region of the complementary complex between a target NA and the addressed oligonucleotide. A such oligonucleotide could be useful for modifying the target NA if the nucleophilic sites of its single-stranded 3'-terminal region are protected due to a specific tertiary structure. A molecular mechanical modelling suggested that the insertion of two additional methylene groups into the standard linker provides an optimal increase in the efficiency of the modification of the base sites exposed into the major groove of the complementary complex. Synthesis of an oligonucleotide derivative with the modified linker and experiments on the target alkylation showed a 2-3 fold increase of the modifying ability as compared with the reagent having the standard linker. The conformational dynamics of the reactive group is discussed.