Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding.
Nat Commun
; 9(1): 3496, 2018 08 29.
Article
em En
| MEDLINE
| ID: mdl-30158518
ABSTRACT
DNA 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-tripodâTel26 complex structures in solution. We solve the 11 and the unique dimeric 42 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 42 structure interlocked by an AA 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos Organoplatínicos
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Platina
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Soluções
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Quadruplex G
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article