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

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 condu...

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Publicado en:Journal of the American Chemical Society Vol. 130; no. 7; pp. 2336 - 2344
Autores principales: Leconte, Aaron M., Gil Tae Hwang, Matsuda, Shigeo, Capek, Petr, Han, Yoshiyuki, Romesberg, Floyd E.
Formato: Artículo
Publicado: American Chemical Society 2/20/2008
Materias:
Acceso en línea:Ver este registro en EBSCOhost
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      pub: American Chemical Society
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        10.1021/ja078223d
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        atl: Discovery, Characterization, and Optimization of an Unnatural Base Pair for Expansion of the Genetic Alphabet.
      aug:
        au:
          Leconte, Aaron M.
          Gil Tae Hwang
          Matsuda, Shigeo
          Capek, Petr
          Han, Yoshiyuki
          Romesberg, Floyd E.
        affil: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037
      su:
        Genes
        Genetic code
        Nucleotide analysis
        DNA polymerases
        Nucleotide sequence
        Biotechnology
      sug:
        subj:
          Genes
          Genetic code
          Nucleotide analysis
          DNA polymerases
          Nucleotide sequence
          Biotechnology
      ab: 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.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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