Sequence-selective minor groove recognition of a DNA duplex containing synthetic genetic components
Padroni, Giacomo and Withers, Jamie M. and Taladriz Sender, Andrea and Reichenbach, Linus F. and Parkinson, John A. and Burley, Glenn A. (2019) Sequence-selective minor groove recognition of a DNA duplex containing synthetic genetic components. Journal of the American Chemical Society, 141 (24). pp. 9555-9563. ISSN 1520-5126 (https://doi.org/10.1021/jacs.8b12444)
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Abstract
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.
ORCID iDs
Padroni, Giacomo ORCID: https://orcid.org/0000-0002-1406-4449, Withers, Jamie M. ORCID: https://orcid.org/0000-0002-9746-9467, Taladriz Sender, Andrea ORCID: https://orcid.org/0000-0002-8274-4761, Reichenbach, Linus F. ORCID: https://orcid.org/0000-0002-9977-0659, Parkinson, John A. ORCID: https://orcid.org/0000-0003-4270-6135 and Burley, Glenn A.;-
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Item type: Article ID code: 68039 Dates: DateEvent19 June 2019Published22 May 2019Published Online22 May 2019Accepted2019SubmittedSubjects: Science > Chemistry Department: Faculty of Science > Pure and Applied Chemistry Depositing user: Pure Administrator Date deposited: 24 May 2019 11:17 Last modified: 06 Oct 2024 00:33 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/68039