{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:59:54Z","timestamp":1790009994140,"version":"4.0.1"},"reference-count":64,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["CRG\/2021\/004525"],"award-info":[{"award-number":["CRG\/2021\/004525"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["IIRPIG\u20102024 122301\u201001128"],"award-info":[{"award-number":["IIRPIG\u20102024 122301\u201001128"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Telomeric repeat\u2013containing RNA (TERRA) plays a central role in telomere maintenance in telomerase\u2010negative cancers that employ the alternative lengthening of telomeres (ALT) pathway; however, its RNA G\u2010quadruplex (rG4) structures remain underexplored as chemical targets. Here, we report a structure\u2010guided approach to selectively modulate TERRA rG4 using an indoloquinoxaline\u2010based small\u2010molecule scaffold. Biophysical analyses confirm high\u2010affinity and selective binding, while NMR and computational studies identify terminal tetrad stacking as the dominant binding mode of the ligand to the TERRA rG4. Ligand engagement disrupts the TERRA\u2013Telomeric Repeat\u2010Binding Factor 2 (TRF2) interaction (ELISA, EMSA) and alters TERRA abundance (qRT\u2010PCR). Transcriptomic (RNA\u2010seq) analysis reveals ligand\u2010induced differential expression of ALT\u2010associated genes and DNA metabolism pathways. In ALT\u2010positive U2OS cells, the ligand localizes to the nucleus, induces telomere\u2010associated DNA damage, and triggers S\u2010phase arrest and apoptosis. These findings establish TERRA rG4 as a chemically addressable structural element in ALT biology and demonstrate the potential of small molecules to probe and modulate long non\u2010coding RNA (lncRNA)\u2010mediated genome maintenance.<\/jats:p>","DOI":"10.1002\/anie.2898522","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:01:06Z","timestamp":1790006466000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Small Molecule Modulation of TERRA RNA Quadruplex Reprograms ALT\u2010Telomere Maintenance"],"prefix":"10.1002","author":[{"given":"Tathagato","family":"Bhattacharyya","sequence":"first","affiliation":[{"name":"School of Chemical Sciences Institution: Indian Association for the Cultivation of Science  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6142-7118","authenticated-orcid":false,"given":"Sarmistha","family":"Pal","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences Institution: Indian Association for the Cultivation of Science  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7761-6088","authenticated-orcid":false,"given":"Maximillian","family":"Braun","sequence":"additional","affiliation":[{"name":"Center for Biomolecular Magnetic Resonance (BMRZ) Institution: Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4884-7772","authenticated-orcid":false,"given":"Sayantan","family":"Pradhan","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences Institution: Indian Association for the Cultivation of Science  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Paul","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences Institution: Indian Association for the Cultivation of Science  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kushal","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences Institution: Indian Association for the Cultivation of Science  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5693-7909","authenticated-orcid":false,"given":"Harald","family":"Schwalbe","sequence":"additional","affiliation":[{"name":"Center for Biomolecular Magnetic Resonance (BMRZ) Institution: Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4130-2841","authenticated-orcid":false,"given":"Jyotirmayee","family":"Dash","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences Institution: Indian Association for the Cultivation of Science  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2848"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010016\u20100324\u2010x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010020\u201001405\u2010w"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010017\u20102573\u20102"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes7060022"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1220"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.03.003"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20104658.2009.07464.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.07.032"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.166"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001177107"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2017.58"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12534"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8030246"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.10528"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1346005"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-032918-021921"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.01.036"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201082406\u2010x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja305734x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u20100236\u2010x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010020\u201000391\u20106"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15071945"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23716-6"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15072178"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201055537\u20105"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf1300"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6379"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010020\u201000637\u20103"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2021.03.003"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2017.09.015"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b04506"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb500100z"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201408113"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910315"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja109767y"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2024.06.003"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010023\u201002633\u20100"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202512715"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky385"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c00736"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5CB00046G"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202401748"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201206281"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2012.682725"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/narmme\/ugaf027"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja806592z"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.06.025"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq296"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14844"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0294236"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2020.06.040"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.02.001"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6220"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa199"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.06.043"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.03.011"},{"key":"e_1_2_8_59_1","first-page":"E5940","volume":"114","author":"Pan X.","year":"2017","journal-title":"Proceedings National Academy of Science USA"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124245"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201024097\u20106"},{"key":"e_1_2_8_62_1","first-page":"4175","article-title":"Telomerase\u2010Negative Immortalized Human Cells Contain a Novel Type of Promyelocytic Leukemia (PML) Body1","volume":"59","author":"Yeager T. R.","year":"1999","journal-title":"Cancer Research"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.12.030"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.4161\/nucl.20326"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3078"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.2898522","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.2898522","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.2898522","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:01:07Z","timestamp":1790006467000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.2898522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":64,"alternative-id":["10.1002\/anie.2898522"],"URL":"https:\/\/doi.org\/10.1002\/anie.2898522","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"assertion":[{"value":"2026-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2898522"}}