Oligonucleotide analysis with MALDI-ion-mobility-TOFMS

Abstract

Matrix-assisted laser-desorption ionization followed by ion-mobility separation and time-of-flight mass analysis (MALDI-IM-TOFMS) has been used to characterize native and chemically modified DNA oligonucleotides up to eight bases in length. Mobility resolution between 20 and 30 can be used to separate oligonucleotides of different length, but not to differentiate between isomers or even different compositions of the same length. MALDI-IM-TOFMS does, however, have additional utility in the analysis of mixtures of DNA oligonucleotides and peptides, because these classes of molecules can be distinguished on the basis of differences in their mobility. Oligonucleotide sequencing is also possible by MALDI-IM-TOFMS. Ion signals corresponding to nucleobase losses, w-type, and y-type fragments were identified by use of differences in ion mobility. MALDI-IM-TOFMS was also used to resolve DNA-platinum adducts from the corresponding unmodified oligonucleotides.