Institute for Organic Chemistry and Chemical Biology, Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt/Main, Max-von-Laue-Strasse 7, 60439, Frankfurt, Germany.
Dipartimento di Chimica "Ugo Schiff", Università degli Studi di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino (FI), Italy.
Angew Chem Int Ed Engl. 2017 Jun 12;56(25):7102-7106. doi: 10.1002/anie.201702135. Epub 2017 May 19.
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.
端粒 G-四链体最近已成为癌症研究中的药物靶点。在此，我们展示了首个配体结合状态下具有生物相关杂交-2 构象的端粒 DNA G-四链体的 NMR 结构。我们通过稳定 G-四链体的金属有机金（III）配体解决了该复合物。对游离和结合结构的分析揭示了 G-四链体盖帽区域的结构变化。配体夹在一个末端 G-四联体和一个侧翼核苷酸之间。与其他处于不同构象的 G-四链体相比，这种复合物结构涉及到主要的结构重排，否定了简单的对接方法在配体-G-四链体结构确定中的应用。
