Efforts to expand the genetic alphabet: identification of a replicable unnatural DNA self-pair

J Am Chem Soc. 2004 Jun 9;126(22):6923-31. doi: 10.1021/ja049961u.

Abstract

Six unnatural nucleotides featuring fluorine-substituted phenyl nucleobase analogues have been synthesized, incorporated into DNA, and characterized in terms of the structure and replication properties of the self-pairs they form. Each unnatural self-pair is accommodated in B-form DNA without detectable structural perturbation, and all are thermally stable and selective to roughly the same degree. Furthermore, the efficiency of polymerase-mediated mispair synthesis is similar for each unnatural nucleotide in the template. In contrast, the efficiency of polymerase-mediated self-pair extension is highly dependent on the specific fluorine substitution pattern. The most promising unnatural base pair candidate of this series is the 3-fluorobenzene self-pair, which is replicated with reasonable efficiency and selectivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Pairing*
  • Base Sequence
  • Circular Dichroism
  • DNA / chemistry*
  • DNA / genetics
  • DNA / metabolism*
  • DNA Replication*
  • DNA-Directed DNA Polymerase / metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Polyphosphates / metabolism
  • Templates, Genetic
  • Thermodynamics

Substances

  • Polyphosphates
  • DNA
  • DNA-Directed DNA Polymerase
  • triphosphoric acid