Dissecting the specificity of sugar code recognition - Unleashing the biomedical potential of galectins by protein...

The cell surface is extremely rich in multilayered information that exists in the form of complex monosaccharide assemblies, establishing a cellular sugar code. The sugar code is specifically deciphered by extracellular lectins, galectins, which are capable of recognizing sugar code components and transforming the code into precise cellular activities. Galectin-dependent reading of the sugar code relies on two major features: the specific recognition of sugars by the galectins' carbohydrate recognition domains (CRDs) and the modular architecture of galectins or their oligomerization. These two characteristics of galectins are essential for most of galectins' functions, as they ensure the specificity of sugar code recognition and permit multivalent interactions with carbohydrate ligands. The natural galectins are characterized by relatively fixed modular architecture, which allows for evolutionarily defined reading of the sugar code, limiting the spectrum of biological activities of galectins. Distinct protein engineering approaches, like linker modulation, crosslinking, domain swapping or fusion with oligomerization scaffolds allow for the modulation of galectin multivalency in order to overcome the natural decoding limitations of galectins and permit alternative reading of the sugar code. In this review, we we provide an overview of the architectures of engineered galectins with altered valency and discuss how alternative reading of the code by such proteins may prove beneficial in biotechnology.