Data di Pubblicazione:
2023
Citazione:
Tumor Carbohydrate Associated Antigen Analogs as Potential Binders for Siglec-7 / C. Di Carluccio, F. Milanesi, M. Civera, C. Abreu, S. Sattin, O. Francesconi, A. Molinaro, O. Vanek, R. Marchetti, A. Silipo. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - 26:40(2023), pp. 1-8. [10.1002/ejoc.202300644]
Abstract:
We investigated two recently synthesized and characterized sialyl derivatives, bearing the Neu5Ac-a-(2-6)-Gal epitope, as promising binders for Siglec-7, an inhibitory Siglec mainly found on natural killer cells. A variety of sialoglycan structures can be recognized by Siglec-7 with implications in the modulation of immune responses. Notably, overexpression of sialylated glycans recognized by Siglec-7 can be associated with the progression of several tumors, including melanoma and renal cell carcinoma. NOE-based NMR techniques, including Saturation Transfer Difference and transferred-NOESY NMR, together with molecular docking and dynamic simulations were combined to shed light on the molecular basis of Siglec-7 recognition of two conformationally constrained Sialyl-Tn antigen analogs. We, therefore, identify the ligands epitope mapping and their conformational features and propose 3D models accurately describing the protein-ligand complexes. We found that the binding site of Siglec-7 can accommodate both synthetic analogs, with the sialic acid mainly involved in the interaction. Moreover, the flexibility of Siglec-7 loops allows a preferred accommodation of the more rigid compound bearing a biphenyl moiety at position 9 of the sialic acid that contributed to the interaction to a large extent. Our findings provided insights for developing potential novel high affinity ligands for Siglec-7 to hinder tumor evasion.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
computational studies; molecular binding; sialo-derivatives; siglecs; NMR spectroscopy
Elenco autori:
C. Di Carluccio, F. Milanesi, M. Civera, C. Abreu, S. Sattin, O. Francesconi, A. Molinaro, O. Vanek, R. Marchetti, A. Silipo
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