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Solution structure for the unique dimeric 4:2 complex of a platinum(II)-based tripod bound to a hybrid-1 human telomeric G-quadruplexSolution structure for the unique dimeric 4:2 complex of a platinum(II)-based tripod bound to a hybrid-1 human telomeric G-quadruplex
Structural highlights
Publication Abstract from PubMedDNA G-quadruplexes are not only attractive drug targets for cancer therapeutics, but also have important applications in supramolecular assembly. Here, we report a platinum(II)-based tripod (Pt-tripod) specifically binds the biological relevant hybrid-1 human telomeric G-quadruplex (Tel26), and strongly inhibits telomerase activity. Further investigations illustrate Pt-tripod induces the formation of monomeric and multimeric Pt-tripodTel26 complex structures in solution. We solve the 1:1 and the unique dimeric 4:2 Pt-tripod-Tel26 complex structures by NMR. The structures indicate preferential binding of Pt-tripod to the 5'-end of Tel26 at a low Pt-tripod/Tel26 ratio of 0-1.0. After adding more Pt-tripod, the Pt-tripod binds the 3'-end of Tel26, unexpectedly inducing a unique dimeric 4:2 structure interlocked by an A:A non-canonical pair at the 3'-end. Our structures provide a structural basis for understanding the dynamic binding of small molecules with G-quadruplex and DNA damage mechanisms, and insights into the recognition and assembly of higher-order G-quadruplexes. Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding.,Liu W, Zhong YF, Liu LY, Shen CT, Zeng W, Wang F, Yang D, Mao ZW Nat Commun. 2018 Aug 29;9(1):3496. doi: 10.1038/s41467-018-05810-4. PMID:30158518[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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