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Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound
Thrombin Binding Aptamer (TBA) is a monomolecular well-defined two G-tetrad antiparallel G-quadruplex DNA that inhibits the activity of human α-thrombin. In this report, we synthesized a quasi-cross-shaped platinum(ii) compound (L′(2)LPt) with one cyclometalated and two carbene ligands. We found L′(...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297526/ https://www.ncbi.nlm.nih.gov/pubmed/35919711 http://dx.doi.org/10.1039/d2sc01196d |
Sumario: | Thrombin Binding Aptamer (TBA) is a monomolecular well-defined two G-tetrad antiparallel G-quadruplex DNA that inhibits the activity of human α-thrombin. In this report, we synthesized a quasi-cross-shaped platinum(ii) compound (L′(2)LPt) with one cyclometalated and two carbene ligands. We found L′(2)LPt has selective affinity to bind the TBA G-quadruplex. A fibrinogen clotting assay revealed that L′(2)LPt can abrogate the inhibitory activity of TBA against thrombin. We solved the 1 : 1 L′(2)LPt–TBA complex structure by NMR, which revealed a unique self-adaptive property of L′(2)LPt upon binding to TBA. In the complex, a carbene ligand of L′(2)LPt rotates to pair with the cyclometalated ligand to form a plane stacking over half of the TBA G-tetrad and covered by lateral TT loops. It is notable that the heavy atom Pt stays out of the G-tetrad. Meanwhile, the other carbene ligand remains relatively perpendicular and forms a hydrogen bond with a guanine to anchor the L′(2)LPt position. This structure exhibits a quasi-cross-shaped Pt(ii) compound bound to the G-quadruplex with an unusual “wall-mounted” binding mode. Our structures provide insights into the specific recognition of antiparallel G-quadruplex DNA by a self-adaptive Pt(ii) compound and useful information for the design of selective G-quadruplex targeting non-planar molecules. |
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