Biopolym. Cell. 1989; 5(1):102-105.
Short Communications
Octathymidylate methylphosphonate alkylating derivatives
1Amirkhanov N. V., 1Zarytova V. F.
  1. Institute of Bioorganic Chemistry, Siberian Branch of the Academy of Sciences of the USSR
    Novosibirsk, USSR


A series of novel derivatives of the oligonucleotide methylphosphonate analogues which alkylate nucleic acids have been synthesized. The following octathymidylate analogues containing 4-[ (N-2-chloroethyl, N-methyl) amino] benzylamine residue (C1RCH2NH—) at 3'-termin were obtained: (I) — (Tp)8NHCH2RCl —phosphodiester oligonucleotide derivative, (II) — TP[TpTp'(CH3)]3TpNHCH2RCl and (III) — Tp[TpTp"(GH3)]3 TpNHCH2RCl — two individual diastereomer derivatives (p' and p") with alternating methylphosphonate and phosphodiester groups, (IV) — Tp[TpTp(CH3)]3NHCH2RCl — a mixture of diastereomers containing three methylphosphonate groups, (V) — Tp[Tp(CH3)]6TpNHCHzRCl —a mixture of diastereomers containing six methylphosphonate groups. Complementary target 5'[32P]dpC5A8C5 is alkylated by the reagents (I) —(V) at 5°, 15°, 20°, 25°, 25°, 30°, 35°, and 40° C. It is shown that derivative (II) is the most effective alkylating reagent within the range of 20-H 35 °C.


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