{
  "abstract": "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-1 but induce opposite thermal responses. TMPyP4 stabilizes the quadruplex (+9 °C), whereas PL7 destabilizes it (-6 °C) 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-quadruplex interactions.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemical and Geological Sciences, University of Cagliari & CSGI, Cittadella Universitaria, S.S. 554 bivio Sestu, 09042Monserrato (Cagliari), Italy.",
    "Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Via Vienna 2, Sassari07100, Italy.",
    "Jerzy Haber Institute of Catalysis and Surface Chemistry Polish Academy of Sciences, Krakow30-239, Poland."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Cristina Carucci",
      "orcid": "0000-0001-8660-788X"
    },
    {
      "affs": [
        0
      ],
      "name": "Monica Mura"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesca Cherchi"
    },
    {
      "affs": [
        1
      ],
      "name": "Giuseppe Satta"
    },
    {
      "affs": [
        0
      ],
      "name": "Aamir Saeed"
    },
    {
      "affs": [
        2
      ],
      "name": "Barbara Jachimska",
      "orcid": "0000-0002-2445-7318"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesca Mocci",
      "orcid": "0000-0003-1394-9146"
    },
    {
      "affs": [
        1
      ],
      "name": "Massimo Carraro",
      "orcid": "0000-0003-2712-6132"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrea Salis",
      "orcid": "0000-0001-5746-2693"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eq53y8azyamww.bib",
  "cited_by": 0,
  "doi": "10.1021/acs.jpclett.6c02493",
  "fulltext_url": "https://europepmc.org/articles/PMC13618040",
  "id": "eq53y8azyamww",
  "issns": [
    "1948-7185"
  ],
  "landing_url": "https://europepmc.org/article/MED/42917869",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|DNA and Nucleic Acid Chemistry"
    ]
  ],
  "openalex": "W7212931237",
  "pdf_url": "https://europepmc.org/articles/PMC13618040?pdf=render",
  "pmcid": "PMC13618040",
  "pmid": "42917869",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/eq53y8azyamww.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42917869",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42917869"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA and Nucleic Acid Chemistry",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Binding Does Not Mean Stabilizing: High-Affinity Porphyrins Exhibit Opposite Effects on G-Quadruplex Stability.",
  "title_text": "Binding Does Not Mean Stabilizing: High-Affinity Porphyrins Exhibit Opposite Effects on G-Quadruplex Stability.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/eq53y8azyamww",
  "venue": "The journal of physical chemistry letters",
  "versions": []
}