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Solution NMR Structure of a Ligand/Hybrid‐2‐G‐Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding
Author(s) -
WirmerBartoschek Julia,
Bendel Lars Erik,
Jonker Hendrik R. A.,
Grün J. Tassilo,
Papi Francesco,
Bazzicalupi Carla,
Messori Luigi,
Gratteri Paola,
Schwalbe Harald
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201702135
Subject(s) - g quadruplex , ligand (biochemistry) , chemistry , stereochemistry , nuclear magnetic resonance spectroscopy , docking (animal) , two dimensional nuclear magnetic resonance spectroscopy , dna , crystallography , biochemistry , medicine , receptor , nursing
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.