N2-Substituted 2′-Deoxyguanosine Triphosphate Derivatives as Selective Substrates for Human DNA Polymerase κ

A. S.Prakasha Gowda, Marietta Lee, Thomas E. Spratt

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

N2-Alkyl-2′-deoxyguanosine triphosphate (N2-alkyl-dGTP) derivatives with methyl, butyl, benzyl, or 4-ethynylbenzyl substituents were prepared and tested as substrates for human DNA polymerases. N2-Benzyl-dGTP was equal to dGTP as a substrate for DNA polymerase κ (pol κ), but was a poor substrate for pols β, δ, η, ι, or ν. In vivo reactivity was evaluated through incubation of N2-4-ethynylbenzyl-dG with wild-type and pol κ deficient mouse embryonic fibroblasts. CuAAC reaction with 5(6)-FAM-azide demonstrated that only cells containing pol κ were able to incorporate N2-4-ethynylbenzyl-dG into the nucleus. This is the first instance of a Y-family-polymerase-specific dNTP, and this method could be used to probe the activity of pol κ in vivo.

Original languageEnglish (US)
Pages (from-to)2628-2631
Number of pages4
JournalAngewandte Chemie - International Edition
Volume56
Issue number10
DOIs
StatePublished - 2017

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

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