Covalent Activation of the C-type Lectin DC-SIGN.

ABSTRACT: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a C-type lectin receptor expressed on antigen-presenting cells, crucial for pathogen recognition and immune modulation. The shallow and polar carbohydrate binding site of DC-SIGN presents challenges for ligand design. Here, we explored covalent modification targeting specific lysine residues as a novel strategy to modulate DC-SIGN function. Screening a lysine-targeted electrophilic fragment library using orthogonal functional assays identified two potent activators. Structural analyses via NMR spectroscopy, mass spectrometry and computational modeling confirmed structural perturbations of the carbohydrate recognition domain (CRD) and revealed distinct mechanisms of activation. While both activators

SUBMITTER: Lefebre J 

PROVIDER: S-EPMC12811664 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature