REACTIVE OLIGONUCLEOTIDE DERIVATIVES BEARING METHYLPHOSPHONATE GROUPS. V. ALKYLATING METHYLPHOSPHONATE OCTATHYMIDYLATE DERIVATIVES BEARING A N-(2-HYDROXYETHYL )PHENAZINIUM RESIDUE INCREASE THE EFFICIENCY OF COMPLEMENTARY ADDRESSED MODIFICATION OF DNA-TARGET
N. V. AMIRKHANOV, V. F. ZARYTOVA
Novosibirsk Institute of Bioorganic Chemistry, Siberian Division of the Academy of Sciences of the USSR
Abstract: Efficiency of the intracomplex alkylation of octadecadeoxyribonucleotide d(pC5A8C5) (target) by R p - and Sp-individual diastereomers of the methylphosphonate octathymidy-late 4-(N-methyl-N-2-chloroethylamino) benzyl phosphoramide (—pNHCH2RCl) derivatives bearing an additional N-(2-hydroxyethyl) phenazinium residue (Phn), viz. ClRCH2NHpTp-•(TpTp)3TpNH(CH2)2NHPhn (I) and PhnNH(CH2)2NHpTp(TpTp)3TpNHCH2RCl (II) (p=-OP(O) (CH3)O-), has been investigated. Stabilisation of the complementary complex formed by the target oligonuclcotide and methylphosphonale oligonucleotide derivatives by the Phn group considerably rose the efficiency of the intracomplex alkylation of the target as compared with alkylation by reagents without Phn. R p-isomeric derivatives of (I) and (II) proved to be the most effective alkylating reagents. Specificity of. alkylation of nucleic acid target by reagents (I) and (II) is studied.
Russian Journal of Bioorganic Chemistry 1990, 16 (3):370-378