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Nucleic Acids Symposium Series 2005 49(1):89-90; doi:10.1093/nass/49.1.89
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© 2005 Oxford University Press

Efforts to expand the genetic code

Floyd E. Romesberg

The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA

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.


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