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- Title
N<sup>2</sup>-Substituted 2′-Deoxyguanosine Triphosphate Derivatives as Selective Substrates for Human DNA Polymerase κ.
- Authors
Gowda, A. S. Prakasha; Lee, Marietta; Spratt, Thomas E.
- 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.
- Subjects
DEOXYGUANOSINE derivatives; CHEMICAL derivatives; SUBSTRATES (Materials science); HUMAN DNA; DNA polymerases; METHYL groups
- Publication
Angewandte Chemie, 2017, Vol 129, Issue 10, p2672
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201611607