Structural and kinetic profiling of allosteric modulation of duplex DNA induced by DNA-binding polyamide analogues

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Aman, Khalid and Padroni, Giacomo and Parkinson, John A. and Welte, Thomas and Burley, Glenn A. (2019) Structural and kinetic profiling of allosteric modulation of duplex DNA induced by DNA-binding polyamide analogues. Chemistry - A European Journal, 25 (11). pp. 2757-2763. ISSN 1521-3765 (https://doi.org/10.1002/chem.201805338)

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Abstract

A combined structural and quantitative biophysical profile of the DNA binding affinity, kinetics and sequence-selectivity of hairpin polyamide analogues is described. DNA duplexes containing either target polyamide binding sites or mismatch sequences are immobilized on a microelectrode surface. Quantitation of the DNA binding profile of polyamides containing N-terminal 1-alkylimidazole (Im) units exhibit picomolar binding affinities for their target sequences, whereas 5-alkylthiazole (Nt) units are an order of magnitude lower (low nanomolar). Comparative NMR structural analyses of the polyamide series shows that the steric bulk distal to the DNA-binding face of the hairpin iPr-Nt polyamide plays an influential role in the allosteric modulation of the overall DNA duplex structure. This combined kinetic and structural study provides a foundation to develop next-generation hairpin designs where the DNA-binding profile of polyamides is reconciled with their physicochemical properties.

ORCID iDs

Aman, Khalid, Padroni, Giacomo ORCID logoORCID: https://orcid.org/0000-0002-1406-4449, Parkinson, John A. ORCID logoORCID: https://orcid.org/0000-0003-4270-6135, Welte, Thomas and Burley, Glenn A.;
  • Item type:Article
    ID code:66071
    Dates:
    Date
    Event
    21 February 2019
    Published
    8 November 2018
    Published Online
    7 November 2018
    Accepted
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:12 Nov 2018 12:40
    Last modified:11 Nov 2024 12:09
    URI:https://strathprints.strath.ac.uk/id/eprint/66071
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