Efforts to expand the genetic alphabet: identification of a replicable unnatural DNA self-pair.
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.
Henry
Allison A
AA
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Olsen
Anne Goldbech
AG
Matsuda
Shigeo
S
Yu
Chengzhi
C
Geierstanger
Bernhard H
BH
Romesberg
Floyd E
FE
D020029:Base Pairing; D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011122:Polyphosphates / Q000378:metabolism; D013698:Templates, Genetic; D013816:Thermodynamics
D011122:Polyphosphates; D004247:DNA; D004259:DNA-Directed DNA Polymerase; C005692:triphosphoric acid