On-chip synthesis of MALDI-TOF MS detectable glycan microarrays

Glycan microarrays are a versatile tool for the identification of endogenous ligands and effective inhibitors for lectins, proteins that selectively bind to carbohydrates. These devices are usually obtained through the covalent immobilization on a surface of a library of glycans which are screened towards a target lectin, revealing the entity of the interaction by fluorescence spectroscopy or by SPR technique.1 In recent years, Reichardt and co-workers have demonstrated that glycans microarrays of compounds absorbed through hydrophobic interactions on a lipid-functionalized ITO support enable analysis of the array by MALDI-TOF MS spectrometry (Figure).2 Here we show that this technology also allows on-chip synthesis of unnatural glycan through enzymatic glycosylation with clickable modified sugar donors followed by Cu(I) catalyzed Azido Alkyne Cycloaddition (CuAAC). The resulting array can be characterized by MALDI-TOF MS, to assess the extent of glycan modification.