Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Enhancing Potency and Selectivity of a DC‐SIGN Glycomimetic Ligand by Fragment‐Based Design: Structural Basis

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.
Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal.univ-grenoble-alpes.fr/hal-02414492
Contributeur : Frank Thomas <>
Soumis le : lundi 16 décembre 2019 - 16:19:16
Dernière modification le : mercredi 15 juillet 2020 - 13:02:04

Lien texte intégral

Identifiants

Collections

Citation

Laura Medve, Silvia Achilli, Joan Guzman-Caldentey, Michel Thépaut, Luca Senaldi, et al.. Enhancing Potency and Selectivity of a DC‐SIGN Glycomimetic Ligand by Fragment‐Based Design: Structural Basis. Chemistry - A European Journal, Wiley-VCH Verlag, 2019, 25 (64), pp.14659-14668. ⟨10.1002/chem.201903391⟩. ⟨hal-02414492⟩

Partager

Métriques

Consultations de la notice

246