Discrimination between lectins with similar specificities by ratiometric profiling of binding to glycosylated surfaces; a chemical ‘tongue’ approach

Carbohydrate–lectin interactions dictate a range of signalling and recognition processes in biological systems. The exploitation of these, particularly for diagnostic applications, is complicated by the inherent promiscuity of lectins along with their low affinity for individual glycans which themselves are challenging to access (bio)synthetically. Inspired by how a ‘tongue’ can discriminate between hundreds of flavours using a minimal set of multiplexed sensors and a training algorithm, here individual lectins are ‘profiled’ based on their unique binding profile (barcode) to a range of monosaccharides. By comparing the relative binding of a panel of 5 lectins to 3 monosaccharide-coated surfaces, it was possible to generate a training algorithm that enables correct identification of lectins, even those with similar glycan preferences. This is demonstrated to be useful for discrimination between the cholera and ricin toxin lectins showing the potential of this minimalist approach for exploiting glycan complexity.