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

Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides
Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides
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 ds-DNA 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 ds-DNA 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 ds-DNA sequence relative to the Im-containing hairpin polyamide.
0305-1048
42-53
Padroni, Giacomo
a4149203-2164-4823-912d-15d2a6e72d19
Parkinson, John A.
936c3cab-5606-4dea-b1cb-40b9ad60192c
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Burley, Glenn A.
ccedea82-73a7-454b-b718-b2d6a56ca28b
Padroni, Giacomo
a4149203-2164-4823-912d-15d2a6e72d19
Parkinson, John A.
936c3cab-5606-4dea-b1cb-40b9ad60192c
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Burley, Glenn A.
ccedea82-73a7-454b-b718-b2d6a56ca28b

Padroni, Giacomo, Parkinson, John A., Fox, Keith R. and Burley, Glenn A. (2018) Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides. Nucleic Acids Research, 46 (1), 42-53. (doi:10.1093/nar/gkx1211).

Record type: Article

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 ds-DNA 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 ds-DNA 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 ds-DNA sequence relative to the Im-containing hairpin polyamide.

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More information

Accepted/In Press date: 28 November 2017
e-pub ahead of print date: 29 November 2017
Published date: 9 January 2018

Identifiers

Local EPrints ID: 416288
URI: http://eprints.soton.ac.uk/id/eprint/416288
ISSN: 0305-1048
PURE UUID: 037c8176-3274-4c11-8bb8-86361b1f592a
ORCID for Keith R. Fox: ORCID iD orcid.org/0000-0002-2925-7315

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Date deposited: 11 Dec 2017 17:30
Last modified: 26 Nov 2021 02:33

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Contributors

Author: Giacomo Padroni
Author: John A. Parkinson
Author: Keith R. Fox ORCID iD
Author: Glenn A. Burley

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