NYMC Faculty Publications

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

Journal Title

Angewandte Chemie (International ed.in English)

First Page

2628

Last Page

2631

Document Type

Article

Publication Date

March 2017

Department

Biochemistry and Molecular Biology

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 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.

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