Projects per year
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.
- DNA-binding polyamides
- DNA binding
- polyamide binding
9/02/15 → 8/02/16
Project: Internally funded project
Aman, K., Padroni, G., Parkinson, J. A., Welte, T., & Burley, G. A. (2019). Structural and kinetic profiling of allosteric modulation of duplex DNA induced by DNA-binding polyamide analogues. Chemistry - A European Journal, 25(11), 2757-2763. https://doi.org/10.1002/chem.201805338