Water-Soluble Pyrene Tags Enable the Detection of Carbohydrates by Label-Assisted Laser Desorption/ionisation Mass Spectrometry

Matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) is widely used for the
analysis of biomolecules. Label-assisted laser desorption/ionisation mass spectrometry (LALDI-MS) is
a matrix-free variant of MALDI-MS, in which only analytes covalently attached to a laser
desorption/ionisation (LDI) enhancer are detected. LALDI-MS has shown promise in overcoming
limitations of MALDI-MS in terms of sample preparation and MS analysis. In this work, we have
developed water-soluble pyrene-based LDI reagents (LALDI tags) that can be used for (in situ) labelling
and LALDI-MS analysis of reducing carbohydrates from complex (biological) samples without the need
for additional chemical derivatisation or purification. We have systematically explored the suitability
of four pyrene-based LDI enhancers and three aldehyde-reactive handles, optimised sample
preparation, and exemplified the use of a LALDI tag by the detection of lactose in cow’s milk. These
results demonstrate that LALDI-MS is a promising technique for the analysis of reducing carbohydrates
in biological samples, and pave the way for the development of LALDI-MS for glycomics and
diagnostics.