STUDY OF STRUCTURAL AND ENERGETICAL ASPECTS OF COMPLEMENTARY ADDRESSED MODIFICATION OF NUCLEIC ACIDSBY METHOD OF MOLECULAR MECHANICS. COMFORMATIONAL ABILITIESOF ALKYLATION BY 4-[N-(2-CHLOROETHYL), N-METHYL] AMINOBENZYL-5'-PHOSPHOAMIDE OLIGONUCLEOTIDE DERIVATIVES
VOROBJEV Yu. N.
Novosibirsk Institute of Bioorganic Chemistry, Siberian Division of the Academy of Sciences of the USSR
Abstract:A method of modelling of structural and energetical aspects of complementary addressed modification of nucleic acids (NA) by means of molecular mechanics is developed. Calculation of conformational energy of NA complexes take into account the effect of environmental solvents on the properties of molecule with the help of original approximation of the solvent's statistical model. Relative reactivities of the oligonucleotide derivatives carrying 4-[N-(2-chloroethyl), N-methyl]aminobenzyl groups at the 5'-terminal phosphates in the addressed modification of target NA are calculated. Complexes of target NA with addressed alkylating reagents (NAR) proved to have only two principal optimal conformations T1, T2 serving as stores of states for the formation of reactive conformations. The reagent's active group is oriented along the 3'-end of the target NA in T1 conformation, whereas in T2 conformation its orientation is opposite to that in T1 and along the 5'-end of the target NA. Correspondence of T1 and T2 to the reactive conformations of the NAR complexes determines the effectiveness of alkylations and the reactivity toward the buffer nuc-leophyle. The result of the model calculations qualitatively agree with experimental observations on the position selectivity of alkylation.
Russian Journal of Bioorganic Chemistry 1990, 16 (1):69-82