Reactive oligonucleotide derivatives bearing methylphosphonate groups. VI. The increase in the efficiency of directed effect of the alkylating methylphosphonate oligodeoxyribonucleotide derivatives on nucleic acids in the presence of effectors, 3',5'-bis-N-(2-hydroxyethyl)phenazinium derivatives of oligodeoxyribonucleotides

N. V. Amirkhanov, V. F. Zarytova, A. S. Levina

Novosibirsk Institute of Bioorganic Chemistry, Siberian Division, Academy of Sciences of the USSR

Abstract: Effectors for increasing the efficiency of DNA modification with the alkylating methylphosphonate analogues of oligodeoxyribonucleotides (MFAO) were suggested. Oligodeoxyribonucleotide d(pC₅A₈ACAATG) used as a target DNA treated with alkylating derivatives of octathymidylate having alternating methylphosphonate and phospho-diester internucleotide bonds(both R_p- and S_p-individual diastereoisomers of MFAO were used) and bearing alkylating 4-(N-methyl-N-2-chloroethylamino)benzyl phosphoramide residue atthe3'-end. The reactions were carried out in the presence of an effector, hexa-deoxyribonucleotide derivative PhnNH(CH₂)₂NHpCATTGTpNH(CH₂)₂NHPhn bearing two N-(2-hydroxyethyl)phenazinium (Phn) residues at the 3'- and 5'-ends and being complementary to the part of the target DNA neighbouring with octaadenylate. It was shown that T_m of the duplex formed by the target DNA, octathymidylate and effector is by 7–13°C higher than in the absence of the effector, thus considerably increasing the efficiency of the intracomplex alkylation of the target (e. g., at 40°C, the increase for the reagent based on the R_p-isomer is sixfold). Specificity of the target DNA modification by the MFAO alkylating derivatives in the presence of effector is same as with reagents based on oligodeoxyribonucleotides with natural internucleotide bonds.

Russian Journal of Bioorganic Chemistry 1990, 16 (11):1523-1530

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