Applications of Matrix-Assisted Laser Desorption Ionization In-Source Decay Mass Spectrometry

Matrix-Assisted Laser Desorption Ionization In-Source Decay (MALDI-ISD) Mass Spectrometry is a very powerful tool for providing terminal sequence information of biomolecules with minimal sample preparations. Fragmentation is induced at the position where hydrogen radical transfers from matrix to analyte in the MALDI-ISD process by proposed mechanism. Uniform fragmentation in MALDI-ISD generates relative simple ion spectra of readable sequence ladders with labile modifications retained, which is advantageous over other fragmentation methods such as collision-induced dissociation (CID) for characterizing modifications. MALDI-ISD has been applied to de novo sequencing of a 13.6 kDa protein and fully validate sequences of therapeutic antibodies, showing its promising potential in examining reference sequences of biotherapeutics unambiguously. It has also been successfully applied to the analysis of modifications such as post-translational modifications (PTMs) and PEGylation. Here we discuss the applications of MALDI-ISD in protein sequencing and modification analysis by featuring representative studies in details.