Enhancing Potency and Selectivity of a DC‐SIGN Glycomimetic Ligand by Fragment‐Based Design : Structural Basis
Articolo
Data di Pubblicazione:
2019
Citazione:
Enhancing Potency and Selectivity of a DC‐SIGN Glycomimetic Ligand by Fragment‐Based Design : Structural Basis / L. Medve, S. Achilli, J. Guzman‐caldentey, M. Thépaut, L. Senaldi, A. Le Roy, S. Sattin, C. Ebel, C. Vivès, S. Martin‐santamaria, A. Bernardi, F. Fieschi. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 25:64(2019 Nov), pp. 14659-14668. [10.1002/chem.201903391]
Abstract:
Chemical modification of pseudo-dimannoside ligands guided by fragment-based design allowed for the exploitation of an ammonium-binding region in the vicinity of the mannose-binding site of DC-SIGN, leading to the synthesis of a glycomimetic antagonist (compound 16) of unprecedented affinity and selectivity against the related lectin langerin. Here, the computational design of pseudo-dimannoside derivatives as DC-SIGN ligands, their synthesis, their evaluation as DC-SIGN selective antagonists, the biophysical characterization of the DC-SIGN/16 complex, and the structural basis for the ligand activity are presented. On the way to the characterization of this ligand, an unusual bridging interaction within the crystals shed light on the plasticity and potential secondary binding sites within the DC-SIGN carbohydrate recognition domain.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
carbohydrates; DC-SIGN; glycomimetics; ligand design; virtual screening
Elenco autori:
L. Medve, S. Achilli, J. Guzman‐caldentey, M. Thépaut, L. Senaldi, A. Le Roy, S. Sattin, C. Ebel, C. Vivès, S. Martin‐santamaria, A. Bernardi, F. Fieschi
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