Efforts to expand the genetic code.
In an effort to develop an unnatural base pair with which to expand the genetic code we have examined a wide variety of simple phenyl rings derivatized with methyl, fluoro, or nitrogen. The small aromatic surface of these base pairs should prevent inter-strand intercalation, which is thought to inhibit the polymerase-mediated synthesis of base pairs with larger aromatic surface area. Surprisingly, despite reduced aromatic surface area and hydrogen-bonding potential, some of these base pairs are stable and synthesized with reasonable efficiency. We have also been examining the use of activity-based selection systems to evolve DNA polymerases to more efficiently recognize the unnatural substrates, and our initial successes are described.
Romesberg
Floyd E
FE
The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
D020029:Base Pairing; D003062:Codon; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D019020:Directed Molecular Evolution; D005815:Genetic Code; D019151:Peptide Library; D010636:Phenols / Q000737:chemistry*
D003062:Codon; D019151:Peptide Library; D010636:Phenols; D004247:DNA; D004259:DNA-Directed DNA Polymerase