Skip Navigation

Publication Detail

Title: N2 -Substituted 2'-Deoxyguanosine Triphosphate Derivatives as Selective Substrates for Human DNA Polymerase κ.

Authors: Gowda, A S Prakasha; Lee, Marietta; Spratt, Thomas E

Published In Angew Chem Int Ed Engl, (2017 Mar 01)

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.

PubMed ID: 28140505 Exiting the NIEHS site

MeSH Terms: Animals; DNA-Directed DNA Polymerase/metabolism*; Deoxyguanine Nucleotides/chemical synthesis; Deoxyguanine Nucleotides/chemistry*; Fibroblasts/metabolism; Humans; Mice; Mice, Knockout; Substrate Specificity

Back
to Top