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

Autor(es):Mostrar menos -

Hooper, Catherine A. J. ^[1] ; Cardo, Lucia ^[1] ; Craig, James S. ^[2] ; Melidis, Lazaros ^[2] ; Garai, Aditya ^[1] ; Egan, Ross T. ^[1] ; Sadovnikova, Viktoriia ^[1] ; Burkert, Florian ^[1] ; Male, Louise ^[1] ; Hodges, Nikolas J. ^[1] ; Browning, Douglas F. ^[1] ; Rosas, Roselyne ^[3] ; Liu, Fengbo ^[4] ; Rocha, V, Fillipe ; Lima, Mauro A. ^[5] ; Liu, Simin ^[4] ; Bardelang, David ^[6] ; Hannon, Michael J. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Birmingham, Sch Chem, Birmingham B15 2TT, W Midlands - England

^[2] Univ Birmingham, Phys Sci Hlth Ctr, Birmingham B15 2TT, W Midlands - England

^[3] Aix Marseille Univ, FSCM, Cent Marseille, CNRS, Spectropole, F-13007 Marseille - France

^[4] Wuhan Univ Sci & Technol, State Key Lab Refractories & Met, Sch Chem & Chem Engn, Wuhan 430081 - Peoples R China

^[5] Rocha, Fillipe, V, Univ Fed Sao Carlos, Dept Chem, BR-13565905 Sao Carlos - Brazil

^[6] Aix Marseille Univ, ICI, CNRS, F-13013 Marseille - France

• Tipo de documento: Artigo Científico
• Fonte: Journal of the American Chemical Society; v. 142, n. 49, p. 20651-20660, DEC 9 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 19/11242-1 - Quantificação relativa de enzimas DNA-Topoisomerase em linhagens celulares: estreitamento da correlação citotoxicidade-mecanismo de ação de compostos de coordenação
• Beneficiário: Fillipe Vieira Rocha
• Modalidade de apoio: Auxílio à Pesquisa - Regular