Rotaxanating Metallo-supramolecular Nano-cylinder Helicates to Switch DNA Junction Binding.

Autor: Hooper CAJ; School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Cardo L; School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Craig JS; Physical Sciences for Health Centre, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Melidis L; Physical Sciences for Health Centre, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Garai A; School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Egan RT; School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Sadovnikova V; School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Burkert F; School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Male L; School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Hodges NJ; School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Browning DF; School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom., Rosas R; Aix Marseille Univ, CNRS, Centrale Marseille, FSCM, Spectropole, Marseille 13007, France., Liu F; The State Key Laboratory of Refractories and Metallurgy, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. China., Rocha FV; Department of Chemistry, Federal University of São Carlos, São Carlos 13565-905, Brazil., Lima MA; Department of Chemistry, Federal University of São Carlos, São Carlos 13565-905, Brazil., Liu S; The State Key Laboratory of Refractories and Metallurgy, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. China., Bardelang D; Aix Marseille Univ, CNRS, ICR, Marseille 13013, France., Hannon MJ; School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.; Physical Sciences for Health Centre, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Jazyk: angličtina
Zdroj: Journal of the American Chemical Society [J Am Chem Soc] 2020 Dec 09; Vol. 142 (49), pp. 20651-20660. Date of Electronic Publication: 2020 Nov 20.
DOI: 10.1021/jacs.0c07750
Abstrakt: A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death. While pseudo-rotaxanation does not modify the DNA-binding properties, proper, mechanically-interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbit[10]uril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor guests. The number of branch points can thus afford kinetic control over the drug de-threading and release.
Databáze: MEDLINE
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