Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding

Nature Communications
Wenting LiuZong-Wan Mao

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-tripod‒Tel26 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.

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Citations

Nov 23, 2019·Nucleic Acids Research·Emilia Puig Lombardi, Arturo Londoño-Vallejo
Feb 7, 2020·Chemical Communications : Chem Comm·Fei WangChunyang Cao
Apr 28, 2020·Chemical Communications : Chem Comm·Derrick Jing Yang TanAnh Tuân Phan
Sep 23, 2020·Nucleic Acids Research·Thi Quynh Ngoc NguyenAnh Tuân Phan
Apr 8, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Shu-Wen ShiJin-Gang Liu
Mar 29, 2020·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Dale L AngJanice R Aldrich-Wright
Apr 25, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guanhui WuDanzhou Yang
Aug 1, 2020·Oncogene·Adam N Guterres, Jessie Villanueva
Oct 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Martina Lenarčič ŽivkovićJanez Plavec
Sep 26, 2020·Nucleic Acids Research·Derrick J Y TanAnh Tuân Phan
Nov 10, 2020·International Journal of Biological Macromolecules·Valentina PirotaDaniela Montesarchio
Feb 11, 2021·Pharmaceuticals·Suxing JinXiaoyong Wang
Aug 15, 2020·Chembiochem : a European Journal of Chemical Biology·Oliver BinasHarald Schwalbe
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Mar 8, 2019·ACS Omega·Jonathan DickerhoffDanzhou Yang
Oct 1, 2021·Chemical Reviews·Eric LargyValérie Gabelica
Nov 20, 2021·Chembiochem : a European Journal of Chemical Biology·Heng GaoYong Shao

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Methods Mentioned

BETA
FRET
NMR
PCR
electrophoresis

Software Mentioned

XPLOR
Studio
PLOR
Discovery
Origin
Sparky
Accelrys Discovery Studio
ProteinSimple

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