N²-(p-n-Octylphenyl)dGTP: Synthesis and Inhibitory Activity Against DNA Polymerases

Janis Jansons Department of Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01655, USA

James Stattel Department of Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01655, USA

Annalisa Verri Istituto di Genetica ed Evoluzionistica, CNR, 27100, Pavia, Italy

Joseph Gambino Department of Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01655, USA

Naseema Khan Department of Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01655, USA

Federico Focher Istituto di Genetica ed Evoluzionistica, CNR, 27100, Pavia, Italy

Silvio Spadari Istituto di Genetica ed Evoluzionistica, CNR, 27100, Pavia, Italy

George Wright Department of Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01655, USA

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Abstract

N²-(p-n-Octylphenyl)-2′-deoxyguanosine 5′-triphosphate (OctPdGTP)has been synthesized chemically. OctPdGTP inhibited DNA polymerases (pol) α, δ and ε from calf thymus, with moderate selectivity for pol α. Mechanistic studies on pol α and bacteriophage T4 DNA polymerase revealed competitive and mixed kinetics of OctPdGTP with respect to the substrate dGTP when the enzymes were assayed on activated DNA and oligo dT:poly dA, respectively.

This paper is dedicated to Professor Yoshihisa Mizuno.

Notes

This paper is dedicated to Professor Yoshihisa Mizuno.

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N²-(p-n-Octylphenyl)dGTP: Synthesis and Inhibitory Activity Against DNA Polymerases

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N²-(p-n-Octylphenyl)dGTP: Synthesis and Inhibitory Activity Against DNA Polymerases