Solution NMR structure of a ligand/hybrid-2-G-quadruplex complex reveals rearrangements that affect ligand binding

  • Telomeric G-quadruplexes have recently emerged as drug targets in cancer research. Herein, we present the first NMR structure of a telomeric DNA G-quadruplex that adopts the biologically relevant hybrid-2 conformation in a ligand-bound state. We solved the complex with a metalorganic gold(III) ligand that stabilizes G-quadruplexes. Analysis of the free and bound structures reveals structural changes in the capping region of the G-quadruplex. The ligand is sandwiched between one terminal G-tetrad and a flanking nucleotide. This complex structure involves a major structural rearrangement compared to the free G-quadruplex structure as observed for other G-quadruplexes in different conformations, invalidating simple docking approaches to ligand-G-quadruplex structure determination

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Metadaten
Author:Julia Wirmer-BartoschekORCiD, Lars Erik Bendel, Hendrik R. A. Jonker, J. Tassilo GrünORCiDGND, Francesco Papi, Carla Bazzicalupi, Luigi Messori, Paola Gratteri, Harald SchwalbeORCiDGND
URN:urn:nbn:de:hebis:30:3-513166
DOI:https://doi.org/10.1002/anie.201702135
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/28524432
Parent Title (English):Postprint, zuerst in: Angewandte Chemie International Edition
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2017/05/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/09/25
Tag:DNA-ligand complexes; G-quadruplexes; NMR spectroscopy; drug design; structure elucidation
Volume:56
Issue:25
Page Number:5
First Page:7102
Last Page:7106
Note:
Postprint, zuerst in: Angewandte Chemie International Edition 56.2017, 25, S. 7102-7106, doi: 10.1002/anie.201702135
Gefördert durch: European Union: Horizon 2020. Infrastructure for NMR, EM and X-rays for Translational Research, iNEXT, H2020 Grant # 653706
HeBIS-PPN:453973191
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoDeutsches Urheberrecht