Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides

Giacomo Padroni, John A. Parkinson, Keith R. Fox, Glenn A. Burley

Research output: Contribution to journalArticle

9 Citations (Scopus)
43 Downloads (Pure)

Abstract

This manuscript reports the molecular basis for double-stranded DNA (dsDNA) binding of hairpin polyamides incorporating a 5-alkyl thiazole (Nt) unit. Hairpin polyamides containing an N-terminal Nt unit induce higher melting stabilisation of target dsDNA sequences relative to an archetypical hairpin polyamide incorporating an N-terminal imidazole (Im) unit. However, modification of the N-terminus from Im to Nt-building blocks results in an increase in dsDNA binding affinity but lower G-selectivity. A general G-selectivity trend is observed for Nt-containing polyamide analogues. G-selectivity increases as the steric bulk in the Nt 5-position increases. Solution-based NMR structural studies reveal differences in the modulation of the target DNA duplex of Nt-containing hairpin polyamides relative to the Im-containing archetype. A structural hallmark of an Nt polyamide•dsDNA complex is a more significant degree of major groove compression of the target dsDNA sequence relative to the Im-containing hairpin polyamide.
Original languageEnglish
Pages (from-to)42-53
Number of pages12
JournalNucleic Acids Research
Volume46
Issue number1
Early online date29 Nov 2017
DOIs
Publication statusPublished - 9 Jan 2018

Keywords

  • hairpin polyamides
  • double-stranded DNA (dsDNA)
  • dsDNA binding

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