Efficient Detection of N-sialoglycans in N-glycomics Using Mass Spectrometry by nMatch.

The structural instability and electronegativity of sialic acids make N-sialoglycan profiling challenging. We compared commonly used preparation strategies, including native, acetohydrazide-based derivatization, and permethylation, in N-glycomics with nMatch, an R-based bioinformatics tool that ensures full coverage of the detected N-glycans using mass spectrometry. We demonstrated that permethylation leads to efficient detection of not only N-sialoglycans but also other N-glycans and, therefore, provides a valuable reference for the selection of the appropriate N-glycan preparation strategy in future studies.