{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:10:56Z","timestamp":1790255456197,"version":"4.1.0"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"38","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Binding affinity is often used as a predictor of G-quadruplex (G4) stabilization. Here, we show that ligand binding and quadruplex stabilization can be thermodynamically decoupled. Two closely related tetracationic porphyrins bind the human telomeric G4 with comparable affinities approaching 106 M\u20131 but induce opposite thermal responses. TMPyP4 stabilizes the quadruplex (+9 \u00b0C), whereas PL7 destabilizes it (\u22126 \u00b0C) despite a similar binding free energy. Thermodynamic analysis reveals distinct binding mechanisms, with TMPyP4 association driven primarily by favorable enthalpy and PL7 binding dominated by entropy. Temperature-dependent circular dichroism measurements indicate that PL7 promotes redistribution within the telomeric G4 conformational ensemble rather than stabilization of the native hybrid fold. These findings demonstrate that high affinity does not necessarily imply G4 stabilization and establish affinity and thermal stabilization as independent descriptors of ligand\u2013quadruplex interactions.<\/jats:p>","DOI":"10.1021\/acs.jpclett.6c02493","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:01:34Z","timestamp":1789387294000},"page":"10919-10925","source":"Crossref","is-referenced-by-count":0,"title":["Binding Does\nNot Mean Stabilizing: High-Affinity Porphyrins\nExhibit Opposite Effects on G-Quadruplex Stability"],"prefix":"10.1021","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8660-788X","authenticated-orcid":true,"given":"Cristina","family":"Carucci","sequence":"first","affiliation":[{"name":"University of Cagliari & CSGI, Cittadella Universitaria , , S.S. 554 bivio Sestu , (Cagliari),","place":["Monserrato, Italy, 09042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Mura","sequence":"additional","affiliation":[{"name":"University of Cagliari & CSGI, Cittadella Universitaria , , S.S. 554 bivio Sestu , (Cagliari),","place":["Monserrato, Italy, 09042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cherchi","sequence":"additional","affiliation":[{"name":"University of Cagliari & CSGI, Cittadella Universitaria , , S.S. 554 bivio Sestu , (Cagliari),","place":["Monserrato, Italy, 09042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Satta","sequence":"additional","affiliation":[{"name":"University of Sassari , , Via Vienna 2 , ,","place":["Sassari, Italy, 07100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aamir","family":"Saeed","sequence":"additional","affiliation":[{"name":"University of Cagliari & CSGI, Cittadella Universitaria , , S.S. 554 bivio Sestu , (Cagliari),","place":["Monserrato, Italy, 09042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2445-7318","authenticated-orcid":true,"given":"Barbara","family":"Jachimska","sequence":"additional","affiliation":[{"name":"Jerzy Haber Institute of Catalysis and Surface Chemistry Polish Academy of Sciences , ,","place":["Krakow, Poland, 30-239"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1394-9146","authenticated-orcid":true,"given":"Francesca","family":"Mocci","sequence":"additional","affiliation":[{"name":"University of Cagliari & CSGI, Cittadella Universitaria , , S.S. 554 bivio Sestu , (Cagliari),","place":["Monserrato, Italy, 09042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2712-6132","authenticated-orcid":true,"given":"Massimo","family":"Carraro","sequence":"additional","affiliation":[{"name":"University of Sassari , , Via Vienna 2 , ,","place":["Sassari, Italy, 07100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5746-2693","authenticated-orcid":true,"given":"Andrea","family":"Salis","sequence":"additional","affiliation":[{"name":"University of Cagliari & CSGI, Cittadella Universitaria , , S.S. 554 bivio Sestu , (Cagliari),","place":["Monserrato, Italy, 09042"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"issue":"1","key":"2026092408415974100_cit1","doi-asserted-by":"publisher","first-page":"14432","DOI":"10.1038\/ncomms14432","article-title":"CX-5461 Is a DNA G-Quadruplex Stabilizer with Selective\nLethality in BRCA1\/2 Deficient Tumours","volume":"8","author":"Xu","year":"2017","journal-title":"Nat.\nCommun."},{"issue":"38","key":"2026092408415974100_cit2","doi-asserted-by":"publisher","first-page":"8048","DOI":"10.1039\/C5CC02252E","article-title":"G-Quadruplex\nLigands Exhibit Differential G-Tetrad Selectivity","volume":"51","author":"Le","year":"2015","journal-title":"Chem. 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Am.\nChem. Soc."},{"issue":"1","key":"2026092408415974100_cit28","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.abb.2006.03.027","article-title":"A Thermodynamic\nSignature for Drug-DNA Binding Mode","volume":"453","author":"Chaires","year":"2006","journal-title":"Arch. Biochem.\nBiophys."},{"issue":"1","key":"2026092408415974100_cit29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0003-9861(02)00202-3","article-title":"Thermodynamics\nof Drug-DNA Interactions","volume":"403","author":"Haq","year":"2002","journal-title":"Arch. Biochem. 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Soc."},{"issue":"19","key":"2026092408415974100_cit35","doi-asserted-by":"publisher","first-page":"10399","DOI":"10.3390\/ijms221910399","article-title":"Interaction of 9-Methoxyluminarine\nwith Different G-Quadruplex\nTopologies: Fluorescence and Circular Dichroism Studies","volume":"22","author":"Nowak-Karnowska","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"18","key":"2026092408415974100_cit36","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf953","article-title":"Eps2Fold: A Rapid\nMethod to Characterize G-Quadruplex DNA Structures Using Single Absorbance\nSpectra","volume":"53","author":"Largy","year":"2025","journal-title":"Nucleic Acids Res."},{"issue":"20","key":"2026092408415974100_cit37","doi-asserted-by":"publisher","first-page":"11259","DOI":"10.1093\/nar\/gkaa870","article-title":"BMPQ-1 Binds Selectively\nto (3+1) Hybrid Topologies in Human Telomeric G-Quadruplex Multimers","volume":"48","author":"Gao","year":"2020","journal-title":"Nucleic Acids Res."},{"issue":"16","key":"2026092408415974100_cit38","doi-asserted-by":"publisher","first-page":"9548","DOI":"10.1093\/nar\/gkab681","article-title":"The Beginning and the End: Flanking Nucleotides Induce a Parallel\nG-Quadruplex Topology","volume":"49","author":"Chen","year":"2021","journal-title":"Nucleic Acids Res."},{"issue":"19","key":"2026092408415974100_cit40","doi-asserted-by":"publisher","first-page":"2848","DOI":"10.1002\/cbic.202100127","article-title":"Thermodynamic Stability of G-Quadruplexes: Impact of Sequence and\nEnvironment","volume":"22","author":"Jana","year":"2021","journal-title":"ChemBioChem."}],"container-title":["The Journal of Physical\nChemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jpclett.6c02493","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jpclcd\/article-pdf\/17\/38\/10919\/68497566\/acs.jpclett.6c02493.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jpclcd\/article-pdf\/17\/38\/10919\/68497566\/acs.jpclett.6c02493.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:56:03Z","timestamp":1790254563000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jpclcd\/article\/17\/38\/10919\/5429253\/Binding-Does-Not-Mean-Stabilizing-High-Affinity"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":39,"journal-issue":{"issue":"38","published-online":{"date-parts":[[2026,9,14]]},"published-print":{"date-parts":[[2026,9,24]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jpclett.6c02493","relation":{},"ISSN":["1948-7185"],"issn-type":[{"value":"1948-7185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]}}}