Sequence-selective minor groove recognition of a DNA duplex containing synthetic genetic components

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Abstract

The structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole-imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P·Z base-pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P·Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this synthetic genetic information, relative to a DNA duplex consisting entirely of Watson-Crick base-pairs. Pyrrole-imidazole polyamides bind to a P·Z-containing DNA duplex to form a stable complex, effectively mimicking a G·C pair. A structural hallmark of minor groove recognition of a P·Z pair by a polyamide is the reduced level of allosteric distortion induced by binding of a polyamide to a DNA duplex. Understanding the molecular determinants that influence minor groove recognition of DNA containing synthetic genetic components provides the basis to further develop unnatural base-pairs for synthetic biology applications.

Original languageEnglish
Pages (from-to)9555-9563
Number of pages9
JournalJournal of the American Chemical Society
Volume141
Issue number24
Early online date22 May 2019
DOIs
Publication statusPublished - 19 Jun 2019

Keywords

  • DNA
  • minor groove recognition
  • unnatural base-pairs
  • synthetic biology
  • NMR

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