Z Biotech’s Glycosphingolipid Glycan Array expedites proof-of-concept studies for genetically encoded chemical crosslinkers of carbohydrates.

Protein-carbohydrate interactions play crucial roles in numerous biological processes. However, studying and manipulating these interactions is difficult due to their low binding affinity and non-covalent nature. A recent research published in the Nature Chemistry has made strides in this domain. The researchers developed a method called genetically encoded chemical crosslinking of proteins with sugar (GECX-sugar), which allows for the creation of covalent linkages between proteins and carbohydrates under mild biocompatible conditions. They employed a unique latent bioreactive unnatural amino acid (Uaa) called O-sulfonyl fluoride-O-methyltyrosine (SFY) that contained sulfonyl fluoride to genetically encode proteins. The O-sulfonyl fluoride group forms covalent crosslinks with glycans through proximity-enabled reactivity, effectively reinforcing protein-glycan interactions with an infinite affinity. As an example, the SFY-incorporated Siglec-7 protein was shown to crosslink specifically with its sialoglycan ligand both in vitro and on the surface of cancer cells. This covalent binding enhanced the killing of cancer cells by natural killer cells. The researchers suggest that the genetically encoded chemical crosslinking of proteins to carbohydrates offers a promising solution to address the low affinity and weak interaction typically observed in protein-sugar interactions. The GECX-sugar technology may advance glycobiology research and provide new methods for protein diagnostics and therapeutics by effectively targeting glycan. Furthermore, the potential applications of this technology in glycan-targeted diagnostics and therapeutics could have significant implications for cancer immunotherapy.

ZBiotech’s Glycosphingolipid Glycan Array have helped researchers identifying potential glycan ligands of recombinant Siglec-7 proteins. The availability of this array has enabled scientists to validate the feasibility of enhancing protein-glycan interactions using GECX-sugar technology. By utilizing glycan microarrays, researchers can efficiently and accurately determine the specific glycans that bind to the protein of interest, thus elucidating the precise nature and specificity of the protein-glycan interaction. Consequently, the glycan microarray serves as a critical tool for unraveling crucial aspects of protein-glycan interactions.