In proteomics, MALDI is used for the rapid identification of proteins isolated by using gel electrophoresis: SDS-PAGE, size exclusion chromatography, affinity chromatography, strong/weak ion exchange, isotope coded protein labeling (ICPL), and two-dimensional gel electrophoresis. Peptide mass fingerprinting is the most popular analytical application of MALDI-TOF mass spectrometers. MALDI TOF/TOF mass spectrometers are used to reveal amino acid sequence of peptides using post-source decay or high energy collision-induced dissociation (further use see mass spectrometry).
MALDI-TOF have been used to characterise post-translational modifications. For example, it has been widely applied to study protein methylation and demethylation. However, care must be taken when studying post-translational modifications by MALDI-TOF. For example, it has been reported that loss of sialic acid has been identified in papers when dihydroxybenzoic acid (DHB) has been used as a matrix for MALDI MS analysis of glycosylated peptides. Using sinapinic acid, 4-HCCA and DHB as matrices, S. Martin studied loss of sialic acid in glycosylated peptides by metastable decay in MALDI/TOF in linear mode and reflector mode. A group at Shimadzu Corporation derivatized the sialic acid by an amidation reaction as a way to improve detection sensitivity and also demonstrated that ionic liquid matrix reduces a loss of sialic acid during MALDI/TOF MS analysis of sialylated oligosaccharides. THAP, DHAP, and a mixture of 2-aza-2-thiothymine and phenylhydrazine have been identified as matrices that could be used to minimize loss of sialic acid during MALDI MS analysis of glycosylated peptides. It has been reported that a reduction in loss of some post-translational modifications can be accomplished if IR MALDI is used instead of UV MALDI.
Besides proteins, MALDI-TOF has also been applied to study lipids. For example, it has been applied to study the catalytic reactions of phospholipases. In addition to lipids, oligonucleotides have also been characterised by MALDI-TOF. For example, in molecular biology, a mixture of 5-methoxysalicylic acid and spermine can be used as a matrix for oligonucleotides analysis in MALDI mass spectrometry, for instance after oligonucleotide synthesis.