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The structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole-imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P·Z base-pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P·Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this synthetic genetic information, relative to a DNA duplex consisting entirely of Watson-Crick base-pairs. Pyrrole-imidazole polyamides bind to a P·Z-containing DNA duplex to form a stable complex, effectively mimicking a G·C pair. A structural hallmark of minor groove recognition of a P·Z pair by a polyamide is the reduced level of allosteric distortion induced by binding of a polyamide to a DNA duplex. Understanding the molecular determinants that influence minor groove recognition of DNA containing synthetic genetic components provides the basis to further develop unnatural base-pairs for synthetic biology applications.
|Number of pages||9|
|Journal||Journal of the American Chemical Society|
|Early online date||22 May 2019|
|Publication status||Published - 19 Jun 2019|
- minor groove recognition
- unnatural base-pairs
- synthetic biology
FingerprintDive into the research topics of 'Sequence-selective minor groove recognition of a DNA duplex containing synthetic genetic components'. Together they form a unique fingerprint.
- 4 Finished
Macromolecular construction of DNA networks directed by the flourous effect
1/11/18 → 30/06/22
Macromolecular construction of DNA networks directed by the fluorous effect
Withers, J. & Burley, G.
1/11/18 → 31/10/21
Data for: "Sequence-selective minor groove recognition of a DNA duplex containing synthetic genetic components"
Taladriz Sender, A. (Creator), Withers, J. (Creator), Burley, G. (Creator), Padroni, G. (Creator), Parkinson, J. (Contributor) & Reichenbach, L. F. (Contributor), University of Strathclyde, 8 Jul 2019
DOI: 10.15129/6800623a-662c-4e03-8d0b-e2dd7bd4c399, https://doi.org/10.1021/jacs.8b12444