Biopolym. Cell. 1989; 5(1):102-105.
Short Communications
Octathymidylate methylphosphonate alkylating derivatives
- Institute of Bioorganic Chemistry, Siberian Branch of the Academy of Sciences of the USSR
Novosibirsk, USSR
Abstract
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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References
[1]
Vlasov VV, Godovikov AA, Zarytova VF, Ivanova EM, Knorre DG. Suppression of immunoglobulin synthesis in myeloma MORS 21 cells by an alkylating oligonucleotide derivative complementary to the mRNA coding for light-chain immunoglobulin. Dokl Akad Nauk SSSR. 1984;276(5):1263-5.
[2]
Zarytova VF, Ivanova EM, Karpova GG, Knorre DG, Pichko NP, Ryte AS, Stephanovich LE. Complementary addressed alkylation of poly (A)-fragments of mRNA in Krebs ascites tumor cells. Russian Journal of Bioorganic Chemistry. 1981; 7 (10):1512-22.
[3]
Miller PS, Braiterman LT, Ts'o PO. Effects of a trinucleotide ethyl phosphotriester, Gmp(Et)Gmp(Et)U, on mammalian cells in culture. Biochemistry. 1977;16(9):1988-96.
[4]
Agarwal KL, Riftina F. Synthesis and enzymatic properties of deoxyribooligonucleotides containing methyl and phenylphosphonate linkages. Nucleic Acids Res. 1979;6(9):3009-24.
[5]
Marugg JE, de Vroom E, Dreef CE, Tromp M, van der Marel GA, van Boom JH. Synthesis of nucleic acid methylphosphonates via the 1-hydroxybenzotriazole phosphotriester approach. Nucleic Acids Res. 1986;14(5):2171-85.
[6]
Agris CH, Blake KR, Miller PS, Reddy MP, Ts'o PO. Inhibition of vesicular stomatitis virus protein synthesis and infection by sequence-specific oligodeoxyribonucleoside methylphosphonates. Biochemistry. 1986;25(20):6268-75.
[7]
Miller PS, Dreon N, Pulford SM, McParland KB. Oligothymidylate analogues having stereoregular, alternating ethylphosphonate/phosphodiester backbones. Synthesis and physical studies. J Biol Chem. 1980;255(20):9659-65.
[8]
Miller PS, Annan ND, McParland KB, Pulford SM. Oligothymidylate analogues having stereoregular, alternating ethylphosphonate/phosphodiester backbones as primers for DNA polymerase. Biochemistry. 1982;21(10):2507-12.
[9]
Miller PS, Yano J, Yano E, Carroll C, Jayaraman K, Ts'o PO. Nonionic nucleic acid analogues. Synthesis and characterization of dideoxyribonucleoside methylphosphonates. Biochemistry. 1979;18(23):5134-43.
[10]
Stawinski J, Hozumi T, Narang SA, Bahl CP, Wu R. Arylsulfonyltetrazoles, new coupling reagents and further improvements in the triester method for the synthesis of deoxyribooligonucleotides. Nucleic Acids Res. 1977;4(2):353-71.
[11]
Amirkhanov NV, Kumarev VP, Rivkin MI, Rybakov VN. Solid-phase synthesis of polydeoxyribonucleotides by a modified phosphotriester method. Russian Journal of Bioorganic Chemistry. 1982; 8 (1):126-9.
[12]
Godovikova TS, Zarytova VF, Khalimskaya LM. Reactive phosphamidates of mono- and dinucleotides. Russian Journal of Bioorganic Chemistry. 1986; 12 (4):475-81.
[13]
Zarytova VF, Kutyavin IV, Sil'nikov VN, Shishkin GV. Modification of nucleic acids in stabilized complementary complexes. I. Synthesis of alkylating derivatives of oligodeoxyribonucleotides having a 5'-terminal N-(2-oxy-ethyl)-phenazinium residue. Russian Journal of Bioorganic Chemistry. 1986; 12 (7):911-20.
[14]
Abramova TV, Knorre DG, Lebedev AV, Pichko NP, Fedorova OS. Investigation of diastereomers of non-ionic oligonucleotide analogues. III. Complementary addressed modification of poly(dA) by alkylating derivative synthesized from individual diastereomers of triethyl phosphotriesters of tetrathymidylyluridine. Russian Journal of Bioorganic Chemistry. 1985; 11 (12):1642-9.
