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Cited by 169

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Discovery, Characterization, and Optimization of an Unnatural Base Pair for Expansion of the Genetic Alphabet

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Leconte, Aaron M., Hwang, Gil Tae, Matsuda, Shigeo, Capek, Petr, Hari, Yoshiyuki, Romesberg, Floyd E.·2008·Journal of the American Chemical Society
DOI 10.1021/ja078223d
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Abstract

DNA is inherently limited by its four natural nucleotides. Efforts to expand the genetic alphabet, by addition of an unnatural base pair, promise to expand the biotechnological applications available for DNA as well as to be an essential first step toward expansion of the genetic code. We have conducted two independent screens of hydrophobic unnatural nucleotides to identify novel candidate base pairs that are well recognized by a natural DNA polymerase. From a pool of 3600 candidate base pairs, both screens identified the same base pair, dSICS:dMMO2, which we report here. Using a series of related analogues, we performed a detailed structure-activity relationship analysis, which allowed us to identify the essential functional groups on each nucleobase. From the results of these studies, we designed an optimized base pair, d5SICS:dMMO2, which is efficiently and selectively synthesized by Kf within the context of natural DNA.

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Cited by

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Metadata

Authors
Leconte, A. M., Hwang, G. T., Matsuda, S., Capek, P., Hari, Y., & Romesberg, F. E.
Venue
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Published
2008-01-25
Volume
130
Issue
7
Pages
2336-2343
ISSN
  • 0002-7863 (ISSN-L)
  • 1520-5126
DOI
10.1021/ja078223d
OpenAlex
W2001319413
Cited by
169
References
1
FWCI
6.95
Type
journal article
Language
en
Open access
green

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