The contributions of individual non-covalent interactions of proteins are routinely studied using sitedirected mutagenesis. The nearest equivalent for carbohydrates is the controlled replacement of individual OH-groups with hydrogen or fluorine to reveal which OH-groups are important for binding. Whereas simple deoxygenation is almost always detrimental to binding, deoxy-fluorination (-OH to -F) can potentially provide a more diverse range of effects (Figure ) as fluorine is a hydrogen-bond acceptor surrogate. Furthermore, fluorination enhances CH-p interactions involving adjacent C-H bonds, modifies lipophilicity, and can facilitate attractive multipolar interactions. OH to F replacement has a minimal steric effect and does not significantly alter monosaccharide conformation, reinforced by emerging glycan 3D structures. Fluorination can also lead to unfavourable interaction effects, such as loss of hydrogen bonding, or mismatched dipoles or partial charges. Hence, glycan fluorination has the potential to be a powerful strategy for introducing selectivity and differentiation between proteins that recognise the same glycan. Lewis x (Figure ) is a glycan motif that is a ligand or potential ligand for recognition in numerous contexts with many different proteins. It is the trisaccharide capping sequence of developmentally regulated stagespecific embryonic antigen, SSEA-1, and the L5 antigen involved in early neural development The Lewis x motif is also expressed on tumour cells and present among human milk oligosaccharides and where it has been shown to protect against toxins and pathogens involved in childhood diseases. Lewis x is also expressed on the surface of pathogens such as gastric cancer causing Helicobacter pylori, and Schistosoma mansoni, the causative agent of the life threatening parasitic disease schistosomiasis, affecting over 200 million people worldwide Given the biological importance of Lewis X , it would be desirable, for diagnostic and therapeutic purposes, to have chemical probes that could distinguish between each of the diverse proteins with which this glycan can interact. We envisioned that fingerprint profiles of protein binding could be generated using a library of site-specific deoxyfluorinated analogues or 'glycofluoroforms'. However, the generation of such a library constitutes a formidable synthetic challenge.