TY  - JOUR
A1  - Wirmer-Bartoschek, Julia
A1  - Bendel, Lars Erik
A1  - Jonker, Hendrik R. A.
A1  - Grün, J. Tassilo
A1  - Papi, Francesco
A1  - Bazzicalupi, Carla
A1  - Messori, Luigi
A1  - Gratteri, Paola
A1  - Schwalbe, Harald
T1  - Solution NMR structure of a ligand/hybrid-2-G-quadruplex complex reveals rearrangements that affect ligand binding
T2  - Postprint, zuerst in: Angewandte Chemie International Edition
N2  - 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
KW  - DNA-ligand complexes
KW  - G-quadruplexes
KW  - NMR spectroscopy
KW  - drug design
KW  - structure elucidation
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51316
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-513166
N1  - 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
VL  - 56
IS  - 25
SP  - 7102
EP  - 7106
ER  -