Tetrathiafulvalene‐Labelled Nucleosides and Nucleoside Triphosphates: Synthesis, Electrochemistry and the Scope of Their Polymerase Incorporation into DNA

Abstract

AbstractThe title 5‐substituted pyrimidines (U and C) and 7‐substituted 7‐deazapurines (7‐deazaA and 7‐deazaG) bearing tetrathiafulvelene (TTF) attached through an acetylene linker have been prepared by Sonogashira cross‐coupling of the corresponding 5‐ or 7‐iodo derivatives of nucleosides with 2‐ethynyltetrathiafulvalene. Their subsequent triphosphorylation gave the corresponding nucleoside triphosphates (dNTPs). Square‐wave voltammetry of the TTF‐labelled nucleosides and nucleotides showed two peaks, one at 0.2–0.3 V and the other at around 0.65 V (vs. Ag|AgCl|3 M KCl), which correspond to two reversible one‐electron redox processes in the TTF moiety. Polymerase incorporation of the TTF‐labelled dNTPs into DNA has also been studied. Multiple incorporations were rather problematic and only by using dCTTFTP was efficient primer extension observed with Vent (exo‐)polymerase. Single nucleotide extension was successful with labelled A (dA*TTFTP) and C (dCTTFTP) nucleotides. Inhibition of the polymerase was observed at higher concentrations of dNTTFTPs.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)