Switching DNA Junction Binding ability of metallosupramolecular Nano-cylinder Helicates by rotaxination
In this talk I will be discussing a new class of rotaxane that is created by our research group at the University of Birmingham, UK. this is the first report of this kind of rotaxane. The principle involves inserting a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate into a large cucurbituril macrocycle as the axle.1 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.2 While pseudo-rotaxanation i.e., the capped cylinder without CB10 does not modify the DNAbinding properties, proper, mechanically interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The interesting observation is 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 cucurbituril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor and being available for binding to the Y shaped junction binding. The number of branch points can thus afford kinetic control over the drug de-threading and release.
1. Catherine A. J. Hooper, Lucia Cardo, James S. Craig, Lazaros Melidis, Aditya Garai, Ross Egan, Viktoriia Sadovnikova, Florian Burkert, Louise Male, Nikolas J. Hodges, Douglas F. Browning, Roselyne Rosas, Fengbo Liu, Fillipe V. Rocha, Mauro A. Lima, David Bardelang, Simin Liu and Michael J. Hannon " Rotaxanating metallosupramolecular Nano-cylinder Helicates to Switch DNA Junction Binding " J. Am. Chem. Soc. 2020, 142, 20651-20660.
2. Lucia Cardo, Michael J. Hannon “Non-covalent metallo-drugs: using shape to target DNA and RNA junctions and other nucleic acid structures” 5 Feb 2018, Metallo-drugs: Development and Action of Anticancer Agents. Walter de Gruyter GmbH & Co. KG, p. 303-324 22 p.(Metal Ions in Life Sciences; vol. 18).