Rotaxanating metallo-supramolecular nano-cylinder helicates to switch DNA junction binding

Catherine A. J. Hooper; Lucia Cardo; James S. Craig; Lazaros Melidis; Aditya Garai; Ross T. Egan; Viktoriia Sadovnikova; Florian Burkert; Louise Male; Nikolas J. Hodges; Douglas F. Browning; Roselyne Rosas; Fengbo Liu; Fillipe V Rocha; Mauro A Lima; Simin Liu; David Bardelang; Michael J. Hannon

doi:10.1021/jacs.0c07750

Rotaxanating metallo-supramolecular nano-cylinder helicates to switch DNA junction binding

Catherine A. J. Hooper, Lucia Cardo, James S. Craig, Lazaros Melidis, Aditya Garai, Ross T. Egan, Viktoriia Sadovnikova, Florian Burkert, Louise Male, Nikolas J. Hodges, Douglas F. Browning, Roselyne Rosas, Fengbo Liu, Fillipe V Rocha, Mauro A Lima, Simin Liu, David Bardelang, Michael J. Hannon

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Abstract

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.

Original language	English
Pages (from-to)	20651-20660
Number of pages	10
Journal	Journal of the American Chemical Society
Volume	142
Issue number	49
Early online date	20 Nov 2020
DOIs	https://doi.org/10.1021/jacs.0c07750
Publication status	Published - 9 Dec 2020

Bibliographical note

Funding Information:
This work was funded by the EPSRC Physical Sciences for Health Centre (EP/L016346/1), BBSRC MIBTP (BB/M01116 X/1), the EU DNAREC Marie Curie Training Site (MEST-CT-2005-020842), an EU Marie Curie Fellowship (H2020-MSCA-IF-2018-844145), FAPESP (2019/11242-1), National Natural Science Foundation of China (21871216), and the University of Birmingham. Simulations used the Bluebear and Castles HPC facility (U. Birmingham). F.B. was supported by a student exchange from LMU Munich. We thank the Centre for Chemical and Materials Analysis (U. Birmingham), the EPSRC UK National Crystallography Service at the University of Southampton for the collection of the crystallographic data, Dr. Mirela Pascu (U. Birmingham) for some initial experiments (on L′) and Dr. Tim Barendt, Prof. Zoe Pikramenou (both U. Birmingham), Prof Alexandre Martinez (Ecole Centrale de Marseille), and Prof Benoît Colasson (U. Paris Descartes) for helpful discussions.

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Hooper, C. A. J., Cardo, L., Craig, J. S., Melidis, L., Garai, A., Egan, R. T., Sadovnikova, V., Burkert, F., Male, L., Hodges, N. J., Browning, D. F., Rosas, R., Liu, F., Rocha, F. V., Lima, M. A., Liu, S., Bardelang, D., & Hannon, M. J. (2020). Rotaxanating metallo-supramolecular nano-cylinder helicates to switch DNA junction binding. Journal of the American Chemical Society, 142(49), 20651-20660. https://doi.org/10.1021/jacs.0c07750

@article{846a74ba95014b2f9efc7c717ab2f855,

title = "Rotaxanating metallo-supramolecular nano-cylinder helicates to switch DNA junction binding",

abstract = "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.",

author = "Hooper, {Catherine A. J.} and Lucia Cardo and Craig, {James S.} and Lazaros Melidis and Aditya Garai and Egan, {Ross T.} and Viktoriia Sadovnikova and Florian Burkert and Louise Male and Hodges, {Nikolas J.} and Browning, {Douglas F.} and Roselyne Rosas and Fengbo Liu and Rocha, {Fillipe V} and Lima, {Mauro A} and Simin Liu and David Bardelang and Hannon, {Michael J.}",

note = "Funding Information: This work was funded by the EPSRC Physical Sciences for Health Centre (EP/L016346/1), BBSRC MIBTP (BB/M01116 X/1), the EU DNAREC Marie Curie Training Site (MEST-CT-2005-020842), an EU Marie Curie Fellowship (H2020-MSCA-IF-2018-844145), FAPESP (2019/11242-1), National Natural Science Foundation of China (21871216), and the University of Birmingham. Simulations used the Bluebear and Castles HPC facility (U. Birmingham). F.B. was supported by a student exchange from LMU Munich. We thank the Centre for Chemical and Materials Analysis (U. Birmingham), the EPSRC UK National Crystallography Service at the University of Southampton for the collection of the crystallographic data, Dr. Mirela Pascu (U. Birmingham) for some initial experiments (on L′) and Dr. Tim Barendt, Prof. Zoe Pikramenou (both U. Birmingham), Prof Alexandre Martinez (Ecole Centrale de Marseille), and Prof Beno{\^i}t Colasson (U. Paris Descartes) for helpful discussions.",

year = "2020",

month = dec,

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doi = "10.1021/jacs.0c07750",

language = "English",

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journal = "Journal of the American Chemical Society",

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Hooper, CAJ, Cardo, L, Craig, JS, Melidis, L, Garai, A, Egan, RT, Sadovnikova, V, Burkert, F, Male, L, Hodges, NJ, Browning, DF, Rosas, R, Liu, F, Rocha, FV, Lima, MA, Liu, S, Bardelang, D & Hannon, MJ 2020, 'Rotaxanating metallo-supramolecular nano-cylinder helicates to switch DNA junction binding', Journal of the American Chemical Society, vol. 142, no. 49, pp. 20651-20660. https://doi.org/10.1021/jacs.0c07750

TY - JOUR

T1 - Rotaxanating metallo-supramolecular nano-cylinder helicates to switch DNA junction binding

AU - Hooper, Catherine A. J.

AU - Cardo, Lucia

AU - Craig, James S.

AU - Melidis, Lazaros

AU - Garai, Aditya

AU - Egan, Ross T.

AU - Sadovnikova, Viktoriia

AU - Burkert, Florian

AU - Male, Louise

AU - Hodges, Nikolas J.

AU - Browning, Douglas F.

AU - Rosas, Roselyne

AU - Liu, Fengbo

AU - Rocha, Fillipe V

AU - Lima, Mauro A

AU - Liu, Simin

AU - Bardelang, David

AU - Hannon, Michael J.

N1 - Funding Information: This work was funded by the EPSRC Physical Sciences for Health Centre (EP/L016346/1), BBSRC MIBTP (BB/M01116 X/1), the EU DNAREC Marie Curie Training Site (MEST-CT-2005-020842), an EU Marie Curie Fellowship (H2020-MSCA-IF-2018-844145), FAPESP (2019/11242-1), National Natural Science Foundation of China (21871216), and the University of Birmingham. Simulations used the Bluebear and Castles HPC facility (U. Birmingham). F.B. was supported by a student exchange from LMU Munich. We thank the Centre for Chemical and Materials Analysis (U. Birmingham), the EPSRC UK National Crystallography Service at the University of Southampton for the collection of the crystallographic data, Dr. Mirela Pascu (U. Birmingham) for some initial experiments (on L′) and Dr. Tim Barendt, Prof. Zoe Pikramenou (both U. Birmingham), Prof Alexandre Martinez (Ecole Centrale de Marseille), and Prof Benoît Colasson (U. Paris Descartes) for helpful discussions.

PY - 2020/12/9

Y1 - 2020/12/9

N2 - 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.

AB - 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.

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U2 - 10.1021/jacs.0c07750

DO - 10.1021/jacs.0c07750

M3 - Article

C2 - 33215921

SN - 0002-7863

VL - 142

SP - 20651

EP - 20660

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 49

ER -

Rotaxanating metallo-supramolecular nano-cylinder helicates to switch DNA junction binding

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