NYMC Faculty Publications


N2 -substituted 2'-deoxyguanosine Triphosphate Derivatives as Selective Substrates for Human DNA Polymerase Kappa

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March 2017


Biochemistry and Molecular Biology


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 kappa (pol kappa), but was a poor substrate for pols beta, delta, eta, iota, or nu. In vivo reactivity was evaluated through incubation of N2 -4-ethynylbenzyl-dG with wild-type and pol kappa deficient mouse embryonic fibroblasts. CuAAC reaction with 5(6)-FAM-azide demonstrated that only cells containing pol kappa 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 kappa in vivo.