High mass accuracy analytical applications of Fourier transform ion cyclotron resonance mass spectrometry

Abstract

The performance capabilities of Fourier transform ion cyclotron resonance (FTICR) mass spectrometry are higher than any other type of mass spectrometer, making this technique suitable for a range of analytical applications. Here, FTICR mass spectrometry has been used for the structural analysis of polyketides and nonribosomal peptides, and in the identification of peptide binding sites of ruthenium(II) arene anticancer complexes. In both these applications, methods have been developed involving complementary tandem mass spectrometry techniques, specifically collision activated dissociation (CAD), electron induced dissociation (EID), and electron capture dissociation. In particular, CAD and EID have been shown to be effective in the structural characterisation of polyketides, with a method developed for distinguishing between two isomers of the polyketide lasalocid A. This method has been optimised and extended for application to non-ribosomal peptides enabling detailed structural information to be obtained with very high accuracy. Using CAD and ECD has enabled the identification of amino acids involved in binding ruthenium(II) complexes. Binding to phenylalanine and glutamic acid was observed in this work for the first time; coordination by histidine and methionine was also observed and is in agreement with previous work. Overall, new methods for highly accurate structural characterisation and binding site identification have been successfully designed and implemented