High resolution tandem mass spectrometry for structural biochemistry

Tandem mass spectrometry (MS/MS) is a well-established technique for determining biomolecular primary sequences. The main advantages of MS/MS analysis compared to more traditional sequencing techniques are speed of analysis, sensitivity, high resolution and high mass accuracy. Currently, the highest performance (highest resolution, highest mass accuracy) mass analyzer is the Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The FT-ICR mass analyzer offers several alternative techniques for tandem mass spectrometry: for example heating techniques, such as sustained off-resonance irradiation collision-induced dissociation (SORI-CID), infrared multiphoton dissociation (IRMPD), blackbody infrared radiative dissociation (BIRD), and the recently introduced technique electron capture dissociation (ECD). In this review, we give an overview of FT-ICR theory, instrumentation, and performance. We also describe the different FT-ICR MS/MS techniques and discuss their capabilities and limitations for the structural biochemistry of peptides, proteins, oligonucleotides, carbohydrates, and glycoconjugates. For example, the complementarity of IRMPD and ECD for glycopeptide structural determination is demonstrated.