Nanomolar inhibitor of the galectin-8 N-terminal domain binds via a non-canonical cation-π interaction.

ABSTRACT: Galectin-8 is a tandem-repeat galectin consisting of two distinct carbohydrate recognition domains and is a potential drug target. We have developed a library of galectin-8N inhibitors that exhibit high nanomolar K_d values as determined by a competitive fluorescence polarization assay. A detailed thermodynamic analysis of the binding of D-galactosides to galectin-8N by isothermal titration calorimetry reveals important differences in enthalpic and/or entropic contributions to binding. Contrary to expectations, the binding of 2-O-propargyl-D-galactoside was found to strongly increase the binding enthalpy, whereas the binding of 2-O-carboxymethylene-D-galactoside was surprisingly less enthalpy-driven. The results of our work suggest that the ethynyl group can successfully replace

SUBMITTER: Puric E 

PROVIDER: S-EPMC11850616 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature