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We here investigate conformational transitions of a DNA deoxyguanosine G\u2010quadruplex (G4) induced by binding of a low molecular weight azobenzene derivative. This ligand acts as a photoswitch that triggers conformational rearrangements of the thrombin binding aptamer (TBA) G4 in a reversible manner pending on the photoisomeric state of the ligand (E\u2010 or Z\u2010configuration). We exploit the reversible association\u2010dissociation of the photoactive ligand to extend current real\u2010time NMR experiments, allowing the in\u2010depth characterization of the folding pathways for the ligand association and dissociation processes and induction of G4 refolding. The folding pathway features kinetic partitioning and significant population of G4 folding intermediates.<\/jats:p>","DOI":"10.1002\/anie.4831000","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T10:13:17Z","timestamp":1792836797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time\u2010Resolved Multidimensional NMR Spectroscopy Reveals the Bifurcated Folding Pathway of a Thrombin\u2010Binding DNA G4\u2013Azobenzene Derivative Complex"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0825-983X","authenticated-orcid":false,"given":"Jason","family":"Martins","sequence":"first","affiliation":[{"name":"Institute For Organic Chemistry and Chemical Biology Goethe University Frankfurt  Frankfurt am Main Germany"},{"name":"Center of Biomolecular Magnetic Resonance (BMRZ) Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wirmer\u2010Bartoschek","sequence":"additional","affiliation":[{"name":"Institute For Organic Chemistry and Chemical Biology Goethe University Frankfurt  Frankfurt am Main Germany"},{"name":"Center of Biomolecular Magnetic Resonance (BMRZ) Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5693-7909","authenticated-orcid":false,"given":"Harald","family":"Schwalbe","sequence":"additional","affiliation":[{"name":"Institute For Organic Chemistry and Chemical Biology Goethe University Frankfurt  Frankfurt am Main Germany"},{"name":"Center of Biomolecular Magnetic Resonance (BMRZ) Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201200348"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02261"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00590"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3CB00114H"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b10429"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb\u20102007\u20108\u201011\u2010r239"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.061234.117"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010biochem\u2010060815\u2010014844"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2020.110406"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad574"},{"key":"e_1_2_8_12_1","first-page":"10917","article-title":"Conformational Switch in the Ribosomal Protein S1 Guides Unfolding of Structured RNAs for Translation Initiation","volume":"46","author":"Qureshi N. 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