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

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)

[thumbnail of Aman-CEJ-2018-Structural-and-kinetic-profiling-of-allosteric-modulation-of-duplex-DNA]
Preview
 Text. Filename: Aman_CEJ_2018_Structural_and_kinetic_profiling_of_allosteric_modulation_of_duplex_DNA.pdf
Final Published Version
License: Creative Commons Attribution 4.0 logo
Download (1MB)| Preview

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
CORE (COnnecting REpositories)