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Optimization of unnatural base pair packing for polymerase recognition

Academic Article
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Overview

related to degree

  • Berger, Allison Henry, Ph.D. in Chemistry, Scripps Research 1999 - 2005

authors

  • Matsuda, S.
  • Berger, Allison Henry
  • Romesberg, Floyd

publication date

  • May 2006

journal

  • Journal of the American Chemical Society  Journal

abstract

  • As part of an effort to expand the genetic alphabet, we have been examining the ability of predominately hydrophobic nucleobase analogues to pair in duplex DNA and during polymerase-mediated replication. We previously reported the synthesis and thermal stability of unnatural base pairs formed between nucleotides bearing simple methyl-substituted phenyl ring nucleobase analogues. Several of these pairs are virtually as stable and selective as natural base pairs in the same sequence context. Here, we report the characterization of polymerase-mediated replication of the same unnatural base pairs. We find that every facet of replication, including correct and incorrect base pair synthesis, as well as continued primer extension beyond the unnatural base pair, is sensitive to the specific methyl substitution pattern of the nucleobase analogue. The results demonstrate that neither hydrogen bonding nor large aromatic surface area is required for polymerase recognition, and that interstrand interactions between small aromatic rings may be optimized for replication. Combined with our previous results, these studies suggest that appropriately derivatized phenyl nucleobase analogues represent a promising approach toward developing a third base pair and expanding the genetic alphabet.

subject areas

  • Base Pair Mismatch
  • Base Pairing
  • DNA Replication
  • DNA-Directed DNA Polymerase
  • Hydrophobic and Hydrophilic Interactions
  • Methylation
  • Nucleotides
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Identity

PubMed Central ID

  • PMC2536690

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja057575m

PubMed ID

  • 16683801
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Additional Document Info

start page

  • 6369

end page

  • 6375

volume

  • 128

issue

  • 19

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