{
    "abstract": "Gangliosides, sialylated glycosphingolipids abundant in the nervous system, play crucial roles in neurotransmission, interaction with regulatory proteins, cell-cell recognition, and signaling. Altered gangliosides expression has been correlated with pathological processes, including cancer, inflammatory disorders, and autoimmune diseases. Gangliosides are important endogenous ligands of Siglecs (Sialic acid-binding immunoglobulin-type lectins), I-type lectins mostly expressed by immune cells, that specifically recognize sialylated glycans. Siglec-7, an inhibitory immune receptor on human natural killer cells, represents a potential target for tumor immunotherapy. Notably, the expression of Siglec-7 ligands is high in various cancers, such as pancreatic cancer and melanoma and lead to tumor immune evasion. Siglec-7 binds the disialylated ganglioside GD3, a tumor-associated antigen overexpressed on cancer cells to suppress immune responses. Using a combination of structural biology techniques, including Nuclear Magnetic Resonance (NMR), biophysical, and computational methods, the binding of Siglec-7 to GD3 and Gb3 derivatives is investigated, revealing the importance of ligand conformation in modulating binding energetics and affinity. The greater flexibility of Gb3 derivatives appears to negatively impact binding entropy, leading to lower affinity compared to GD3. A thorough understanding of these interactions could contribute to elucidating molecular mechanisms of cancer immune evasion and facilitate the development of ganglioside-based diagnostic and therapeutic strategies for cancer.",
    "authors": [
        {
            "affiliation": "Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, Naples, 80126, Italy.\nCEINGE-Biotecnologie Avanzate Franco Salvatore, Via Gaetano Salvatore 486, Napoli, 80145, Italy.",
            "firstname": "Cristina",
            "initials": "C",
            "lastname": "Di Carluccio"
        },
        {
            "affiliation": "Magnetic Resonance Centre (CERM), CIRMMP and Department of Chemistry \"Ugo Schiff\", University of Florence, Via Luigi Sacconi 6, Sesto Fiorentino, 50019, Italy.",
            "firstname": "Luis",
            "initials": "L",
            "lastname": "Padilla-Cort\u00e9s"
        },
        {
            "affiliation": "Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, Naples, 80126, Italy.",
            "firstname": "Marta",
            "initials": "M",
            "lastname": "Tiemblo-Mart\u00ecn"
        },
        {
            "affiliation": "Magnetic Resonance Centre (CERM), CIRMMP and Department of Chemistry \"Ugo Schiff\", University of Florence, Via Luigi Sacconi 6, Sesto Fiorentino, 50019, Italy.\nGiotto Biotech s.r.l., Sesto Fiorentino, 50019, Italy.",
            "firstname": "Giulia Roxana",
            "initials": "GR",
            "lastname": "Gheorghita"
        },
        {
            "affiliation": "Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, Naples, 80126, Italy.",
            "firstname": "Rosario",
            "initials": "R",
            "lastname": "Oliva"
        },
        {
            "affiliation": "Magnetic Resonance Centre (CERM), CIRMMP and Department of Chemistry \"Ugo Schiff\", University of Florence, Via Luigi Sacconi 6, Sesto Fiorentino, 50019, Italy.",
            "firstname": "Linda",
            "initials": "L",
            "lastname": "Cerofolini"
        },
        {
            "affiliation": "Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, Naples, 80126, Italy.",
            "firstname": "Alessandro Antonio",
            "initials": "AA",
            "lastname": "Masi"
        },
        {
            "affiliation": "Department of Biochemistry, Faculty of Science, Charles University, Hlavova 2030/8, Prague, 12800, Czech Republic.",
            "firstname": "Celeste",
            "initials": "C",
            "lastname": "Abreu"
        },
        {
            "affiliation": "Department of Chemistry, National Tsing Hua University, Hsinchu, 300044, Taiwan.",
            "firstname": "Hsin-Kai",
            "initials": "HK",
            "lastname": "Tseng"
        },
        {
            "affiliation": "Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, Naples, 80126, Italy.\nCEINGE-Biotecnologie Avanzate Franco Salvatore, Via Gaetano Salvatore 486, Napoli, 80145, Italy.",
            "firstname": "Antonio",
            "initials": "A",
            "lastname": "Molinaro"
        },
        {
            "affiliation": "Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, Naples, 80126, Italy.",
            "firstname": "Pompea",
            "initials": "P",
            "lastname": "Del Vecchio"
        },
        {
            "affiliation": "Department of Biochemistry, Faculty of Science, Charles University, Hlavova 2030/8, Prague, 12800, Czech Republic.",
            "firstname": "Ond\u0159ej",
            "initials": "O",
            "lastname": "Van\u011bk"
        },
        {
            "affiliation": "Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.",
            "firstname": "Chun-Cheng",
            "initials": "CC",
            "lastname": "Lin"
        },
        {
            "affiliation": "Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, Naples, 80126, Italy.",
            "firstname": "Roberta",
            "initials": "R",
            "lastname": "Marchetti"
        },
        {
            "affiliation": "Magnetic Resonance Centre (CERM), CIRMMP and Department of Chemistry \"Ugo Schiff\", University of Florence, Via Luigi Sacconi 6, Sesto Fiorentino, 50019, Italy.",
            "firstname": "Marco",
            "initials": "M",
            "lastname": "Fragai"
        },
        {
            "affiliation": "Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, Naples, 80126, Italy.\nCEINGE-Biotecnologie Avanzate Franco Salvatore, Via Gaetano Salvatore 486, Napoli, 80145, Italy.",
            "firstname": "Alba",
            "initials": "A",
            "lastname": "Silipo"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2025 The Author(s). Advanced Science published by Wiley\u2010VCH GmbH.",
    "doi": "10.1002/advs.202415782",
    "journal": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
    "keywords": [
        "NMR",
        "gangliosides",
        "siglec\u20107",
        "structural biology"
    ],
    "methods": null,
    "publication_date": "2025-04-26",
    "pubmed_id": "40285643",
    "results": null,
    "title": "Insights into Siglec-7 Binding to Gangliosides: NMR Protein Assignment and the Impact of Ligand Flexibility.",
    "xml": "<Element 'PubmedArticle' at 0x788506ea9ee0>"
}