Biopolym. Cell. 1985; 1(6):293-307.
New inhibitors of DNA and RNA biosynthesis in vitro and in vivo
1Babealashvilli R. Sh., 1Chidgeavadze Z. G., 2Krayevsky A. A., 2Kukhanova M. K., 2Atrazhev A. M., 3Azhaev A. V., 2Kutateladze T. V.
  1. Research Institute of Experimental Cardiology, National Cardiological Research Centre, Academy of Medical Sciences of the USSR
    Moscow, USSR
  2. Institute of Molecular Biology, Academy of Sciences of the USSR
    Moscow, USSR
  3. Institute of Physiology, Academy of Sciences of the Georgian SSR,
    Tbilisi, USSR


This review summarizes the authors' data on the pathways of the synthesis and properties of a great number of new inhibitors of DNA and RNA biosynthesis in vitro and in vivo. The molecular mechanism of the action of these inhibitors in the reactions of polymerization, pyrophosphorolysis and hydrolysis is determined using individual templatfts with involvement of purified DNA and RNA polymerases. Some of these inhibitors are shown to be applicable fo studying of replication in the culture of eukaryotic cells, in embryos and cell nuclei, as well as for repairing DNA in chromatin


[1] Suhadolnik RJ. Naturally occurring nucleoside and nucleotide antibiotics. Prog Nucleic Acid Res Mol Biol. 1979;22:193-291.
[2] Aivazashvili VA, Bibilashvili RSh, Florent'ev VL. ATP analogs in the RNA-polymerase reaction. Mol Biol (Mosk). 1977;11(4):854-63.
[3] Axelrod VD, Vartikyan RM, Aivazashvili VA, Beabealashvili RS. Specific termination of RNA polymerase synthesis as a method of RNA and DNA sequencing. Nucleic Acids Res. 1978;5(10):3549-63.
[4] Plach H, Westhof E, L?demann HD, Mengel R. Solution conformational analysis of 2'-amino-2''deoxyadenosine, 3'-amino-3'-deoxyadenosine and puromycin by pulsed nuclear-magnetic-resonance methods. Eur J Biochem. 1977;80(1):295-304.
[5] Westhof E, Plach H, Cuno I, L?demann HD. Proton magnetic resonance studies of 2'-,3'-, and 5'-deoxyadenosine conformations in solution. Nucleic Acids Res. 1977;4(4):939-53.
[6] Azhayev AV, Ozols AM, Bushnev AS, Dyatkina NB, Kochetkova SV, Victorova LS, Kukhanova MK, Krayevsky AA, Gottikh BP. Aminonucleosides and their derivatives. IV. Synthesis of the 3'-amino-3'-deoxynucleoside 5'-phosphates. Nucleic Acids Res. 1979;6(2):625-43.
[7] Ozols AM, Azhayev AV, Dyatkina NB, Krayevsky AA. Aminonucleosides and their derivatives. VI. A new synthesis of l,2,5-tri-0-acyl-3-azido-3-deoxy-p-D-ribofuranose. Synthesis. 1980; 1980(7): 557-559.
[8] Kutateladze T, Beabealashvili R, Azhayev A, Krayevsky A. 3'-deoxy-3'-aminonucleoside 5'-triphosphates--terminators of RNA synthesis, catalyzed by DNA-dependent RNA polymerase from Escherichia coli. FEBS Lett. 1983;153(2):420-6.
[9] Atkinson MR, Deutscher MP, Kornberg A, Russell AF, Moffatt JG. Enzymatic synthesis of deoxyribonucleic acid. XXXIV. Termination of chain growth by a 2',3'-dideoxyribonucleotide. Biochemistry. 1969;8(12):4897-904.
[10] Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors.Proc Natl Acad Sci U S A. 1977;74(12):5463-7.
[11] Smith AJ. DNA sequence analysis by primed synthesis. Methods Enzymol. 1980;65(1):560-80.
[12] Dyatkina NB, Azhayev AV. Aminonuclosides and Their Derivatives; XII 1 . A New Synthesis of 1- O -Methyl-3-azido-2,3-dideoxy-D-ribofuranose. Synthesis. 1984; 1984(11):961-963.
[13] Dyatkina NB, Kpayevsky AA, Azhayev AV, Jartseva IV. Aminonucleotides and Their Derivatives; XIII1. Synthesis of Benzimidazole Azidonucleotides. Synthesis. 1985; 1985(4):410-411.
[14] Zaitseva V. E., Dyatkina N. B., Krayevsky A. A., Skaptsova N. V., Turina O. V., Gnuchev N. V., Gottikh B. P., Azhayev A. V. Aminonucleosides and their derivatives. XI. Synthesis of 3'-amino-2',3'-dideoxynucleoside 5'-triphosphates. Russian Journal of Bioorganic Chemistry. 1984; 10 (5):670-680.
[15] Grosse F, Krauss G. Purification of a 9S DNA polymerase alpha species from calf thymus. Biochemistry. 1981;20(19):5470-5.
[16] Chang LM. Low molecular weight deoxyribonucleic acid polymerase from calf thymus chromatin. I. Preparation of homogeneous enzyme. J Biol Chem. 1973;248(11):3789-95.
[17] Wang TS, Sedwick WD, Korn D. Nuclear deoxyribonucleic acid polymerase. Purification and properties of the homogeneous enzyme from human KB cells. J Biol Chem. 1974;249(3):841-50.
[18] Waser J, H?bscher U, Kuenzle CC, Spadari S. DNA polymerase beta from brain neurons is a repair enzyme. Eur J Biochem. 1979;97(2):361-8.
[19] Chidgeavadze ZG, Beabealashvilli RS, Atrazhev AM, Kukhanova MK, Azhayev AV, Krayevsky AA. 2',3'-Dideoxy-3' aminonucleoside 5'-triphosphates are the terminators of DNA synthesis catalyzed by DNA polymerases. Nucleic Acids Res. 1984;12(3):1671-86.
[20] Messing J, Gronenborn B, M?ller-Hill B, Hans Hopschneider P. Filamentous coliphage M13 as a cloning vehicle: insertion of a HindII fragment of the lac regulatory region in M13 replicative form in vitro. Proc Natl Acad Sci U S A. 1977;74(9):3642-6.
[21] Zaitseva V. E., Skaptsova N. V., Azhayev A. V., Krayevsky A. A. Aminonucleosides and their derivatives. X. 2'-Deoxydinucleoside phosphates and 2'-deoxydinucleotides with phosphoamide bonds. Russian Journal of Bioorganic Chemistry. 1984, 10 (3):401-407.
[22] Krayevsky A, Kukhanova M, Atrazhev A et al. 2'-3'-Dideoxy-3'-aminonucleoside 5'-phosphates are the terminators of DNA synthesis catalyzed by DNA polymerases. Nucl. Acids Res., Symp. Ser., 1984; 14:283-284.
[23] Kukhanova M, Krayevsky A, Terentyeva N, Rasskazov V. Inhibition of replicative DNA synthesis in nuclei of Strongylocentrotus intermedium urchin embryo by 2',3'-dideoxy-3'-aminonucleoside 5'-triphosphates. Biochim Biophys Acta. 1984;783(3):221-6.
[24] Zoncheddu A, Accomando R, Badaraceo G. Comparison of the effects of differential inhibitors of eucaryotic DNA polymerases on DNA synthesis in isolated rat liver nuclei. Int. J. Biochem. 1983; 15(3):337-342.
[25] Waqar MA, Evans MJ, Huberman JA. Effect of 2',3'-dideoxythymidine-5'-triphosphate on HeLa cell in vitro DNA synthesis: evidence that DNA polymerase alpha is the only polymerase required for cellular DNA replication. Nucleic Acids Res. 1978;5(6):1933-46.
[26] Krayevsky A, Kukhanova M, Alexandrova L, Belyakova N, Krutyakov V. 2',3'-Dideoxy-3'-aminonucleoside 5'-triphosphates inhibit the repair of DNA in rat liver chromatin. Biochim Biophys Acta. 1984;783(3):216-20.
[27] Beliakova NV, Naryzhnyi SN, Krutiakov VM. Mechanism of activating action of ATP on repair synthesis of DNA in chromatin. Mol Biol (Mosk). 1980;14(3):586-94.
[28] Miller MR, Lui LH. Participation of different DNA polymerases in mammalian DNA repair synthesis is not related to "patch size". Biochem Biophys Res Commun. 1982;108(4):1676-82.
[29] Krutiakov VM, Kravetskaia TP. Endogenous DNA synthesis in isolated chromatin. Mol Biol (Mosk). 1978;12(3):654-62.
[30] Kochetkova S. V., Kukhanova M. K., Krayevsky A. A. Phosphorylation of 3'-deoxy-3'-aminothymidine in the mouse myeloma p38ag653 cell culture and its incorporation into DNA. Biopolym. Cell. 1985; 1(3):131-134
[31] Kukhanova MK, Kochetkova SV, Kraevskii AA, Terent'ev LL, Rasskazov VA. Inhibition of DNA biosynthesis in sea urchin embryos by 2',3'-dideoxy-3'-aminonucleosides. Biokhimiia. 1983; Oct;48(10):1747-51.