N2‐Substituted 2′‐Deoxyguanosine Triphosphate Derivatives as Selective Substrates for Human DNA Polymerase κ Article Swipe
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· 2017
· Open Access
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· DOI: https://doi.org/10.1002/anie.201611607
· OA: W2583750744
N 2 ‐Alkyl‐2′‐deoxyguanosine triphosphate (N 2 ‐alkyl‐dGTP) derivatives with methyl, butyl, benzyl, or 4‐ethynylbenzyl substituents were prepared and tested as substrates for human DNA polymerases. N 2 ‐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 N 2 ‐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 N 2 ‐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.
