Indirect mass spectrometric methods for characterizing and sequencing oligonucleotides

The use of mass spectrometry for the characterization and sequence determination of oligonucleotides is reviewed. This review focuses primarily on the use of mass spectrometry to analyze sequence‐specific fragments of oligonucleotides that are generated via solution‐phase chemical reactions. The majority of these “indirect” sequencing methods are a result of recent advances in electrospray ionization and matrix‐assisted laser desorption/ionization for the generation of intact gas‐phase ions from oligonucleotides. Descriptions of the current indirect sequencing protocols will be presented as well as a comparison of the applicability of these procedures for analyzing “real world” samples. The applicability of indirect mass spectrometric sequencing to antisense oligonucleotides will be discussed in detail. © 1997 John Wiley & Sons, Inc.