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Structure-functional analysis of interactions of terminal deoxynucleotidyl transferase with new non-nucleoside substrates

Abstract

New non-nucleoside esters of phosphoric acid containing various hydrophobic groups, namely (1) N-(2-tripticencarbonyl)-4-aminobutyl; (2) 5-phenylsubstituted N-(2,4-dinitrophenyl)-4-aminobutyl; (3) N-(4-phenylbenzoyl)- and N-(4-(N-benzylamino)benzoyl)-2-aminoethyl groups, as well as (4) diphenylmethyl and fluorenyl groups were synthesized and studied as substrates of terminal deoxynucleotidyl transferase. With the exception of the two latter derivatives, all the analogues displayed substrate properties and could incorporate into the deoxyoligonucleotide 3′-end. As it was shown in biochemical experiments and by computer modeling, a linker joining the triphosphate and hydrophobic fragments of the molecule was necessary for these compounds to display substrate properties.

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Abbreviations

CDI:

1,1′-dicarbonyldiimidazole

TdT:

terminal deoxynucleotidyl transferase

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Correspondence to A. L. Khandazhinskaya.

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Original Russian Text © E.S. Matyugina, L.A. Alexandrova, M.V. Jasco, A.V. Ivanov, I.A. Vasiliev, V.L. Lapteva, A.L. Khandazhinskaya, M.K. Kukhanova, 2009, published in Bioorganicheskaya Khimiya, 2009, Vol. 35, No. 3, pp. 376–383.

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Matyugina, E.S., Alexandrova, L.A., Jasco, M.V. et al. Structure-functional analysis of interactions of terminal deoxynucleotidyl transferase with new non-nucleoside substrates. Russ J Bioorg Chem 35, 342–348 (2009). https://doi.org/10.1134/S1068162009030091

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  • DOI: https://doi.org/10.1134/S1068162009030091

Key words

  • non-nucleoside substrates
  • substrate properties
  • terminal deoxynucleotidyl transferase
  • triphosphate derivatives