Molecular mechanical study of structural-energetical aspects of the complementary addressed modification of nucleic acids by reactive derivatives of oligonucleotides carrying a 3'-terminal 4-[N-(2-chloroethyl)- N-methylamino]benzyliden group
Yu. N. Vorobjov
Institute of Bioorganic Chemistry, Siberian Division, Academy of Sciences of the USSR, Novosibirsk
Abstract: Calculations of probabilities of the complementary addressed modification of a target nucleic acid by derivatives of oligonucleotides carrying a 4-[N-(2-chloroethyl)-N-methyl]aminobenzylidene group attached to the 3'-end (3'-BDO) have been made. The results show that the complementary complex of a target NA with 3'-BDO having R-configuration of carbon atom of the dioxalane ring is more stable than the complex including the S-stereoisomer. The S- and R-epimeres of 3'-BDO have essentially different positional abilities for alkylation of the target. The R-epimer alkylates best of all the third base of the target NA from terminal complementary pair of the complex. The S-epimer has another site the most sensitive to alkylation, which is a terminal complementary base of the target NA or the adjacent nonpaired base. Formation of the alkylation complexes are accompanied with a loss or a breakdown of hydrogen bonds in the terminal complementary base pair, thus decreasing the efficiency of alkylation. The modeling results are considered along with experimental data on modification, which therefore can be interpreted on the fundamental structural level.
Russian Journal of Bioorganic Chemistry 1991, 17 (2):211-222