The Galβ-(syn)-gauche configuration is required for galectin-recognition disaccharides

Area of Science:

• Glycobiology
• Molecular Biology
• Biochemistry

Background:

• Galectins are animal lectins with diverse carbohydrate-recognition domains (CRDs) involved in numerous physiological processes.
• Previous studies on galectin-saccharide binding affinities used a limited set of oligosaccharides, hindering a complete understanding of recognition rules.
• Fundamental knowledge of galectin sugar-binding specificity across a broader range of oligosaccharides is lacking.

Purpose of the Study:

• To systematically investigate galectin-saccharide binding specificities using an expanded panel of oligosaccharides.
• To establish a comprehensive rule for galectin carbohydrate recognition.
• To differentiate galectins from other lectin families based on binding characteristics.

Main Methods:

• Frontal affinity chromatography (FAC) was employed to analyze binding affinities.
• 142 fluorescently labeled oligosaccharides were used to study human galectins (1-9).
• Binding characteristics were further validated using non-human galectins and other Gal/GalNAc-binding lectins.

Main Results:

• An initial empirical rule, [Galβ-equatorial], was found insufficient for certain structures like the nematode disaccharide 'Galβ1-4-L-Fuc'.
• A refined, ultimate rule for galectin-recognition disaccharides, "Galβ-(syn)-gauche", was established.
• This new rule accurately describes binding for all identified galectins and effectively distinguishes them from other lectins.

Conclusions:

• The established "Galβ-(syn)-gauche" rule provides a foundational understanding of the glyco-code.
• This research facilitates the development of therapeutic inhibitors that mimic galectin ligands.