A robust glycan labeling strategy using a new cationic hydrazide tag for MALDI-MS-based rapid and sensitive glycomics analysis

ABSTRACT Chemical derivatization of glycans is a common strategy to increase the analytical performance of MALDI-MS-based glycan profiling techniques. Hydrazide, one of the most popular tags, offers important advantages including allowing purification-free procedures. Several hydrazides have thus been used for glycomics combined with an on-target strategy to further simplify the analytical procedures. Usually, gentle heating and mildly acidic conditions with somewhat long reaction times are needed for these hydrazide derivatizations to reach a high reaction efficiency, which makes the current hydrazide tags not yet perfectly conducive to high-throughput analysis. To further optimize these hydrazide tags for high-throughput analysis, based on the structure of a reported hydrazide and the theoretical calculations, a new cationic hydrazide tag, 4-(hydrazinecarbonyl)-N,N,N-trimethylbenzenaminium (HTMBA), was designed, synthesized and tested in this work. HTMBA could completely derivatize glycans at room temperature in several seconds under very mildly acidic conditions (