Jump to main content
Jump to site search


2'-Deoxyribonucleoside 5'-triphosphates bearing 4-phenyl and 4-pyrimidinyl imidazoles as DNA polymerase substrates

Abstract

We developed a versatile access to a series of 4-substituted imidazole 2′-deoxyribonucleotides triphosphates bearing functionalized phenyl or pyrimidinyl rings. 4-Iodo-1H-imidazole was enzymatically converted into the corresponding 2'-deoxynucleoside, which was then chemically derived into its 5'-triphosphate, followed by 4-arylation via Suzuki-Miyaura coupling using (hetero)arylboronic acids. Both KF (exo-) and Deep Vent (exo-) DNA polymerases incorporated these modified nucleotides in primer-extension assays, adenine being the preferred pairing partner in the template. The 4-(3-aminophenyl)imidazole derivative (3APh) was the most efficiently inserted opposite A by KF (exo-) with only a 37-fold lower efficiency (Vmax/KM) than that of the correct dTTP. No further extension occurred after the incorporation of a single aryl-imidazole nucleotide. Interestingly, the aryl-imidazole dNTPs were found to undergo successive incorporation by calf thymus terminal deoxynucleotidyltransferase with different tailing efficiencies among this series and with a marked preference for 2APyr polymerization.

Back to tab navigation

Supplementary files

Publication details

The article was received on 03 Oct 2018, accepted on 04 Dec 2018 and first published on 04 Dec 2018


Article type: Paper
DOI: 10.1039/C8OB02464B
Citation: Org. Biomol. Chem., 2018, Accepted Manuscript
  •   Request permissions

    2'-Deoxyribonucleoside 5'-triphosphates bearing 4-phenyl and 4-pyrimidinyl imidazoles as DNA polymerase substrates

    S. Vichier-Guerre, L. Dugué and S. Pochet, Org. Biomol. Chem., 2018, Accepted Manuscript , DOI: 10.1039/C8OB02464B

Search articles by author

Spotlight

Advertisements