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
Download full text files
Additional Services
| Author: | Julia Wirmer-BartoschekORCiD, Lars Erik Bendel, Hendrik R. A. JonkerORCiD, 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): |  Deutsches Urheberrecht |
