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 Rp- and Sp-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 Tm 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 Rp-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