Fundamental Processes in Electron Capture Dissociation: Peptides, Polymers and Fullerenes

Lead Research Organisation: University of Birmingham
Department Name: Sch of Biosciences

Abstract

A molecule's structure defines its reactivity and, in the case of biomolecules, its function. It is therefore important to be able to elucidate molecular structure. Mass spectrometry is a technique which enables measurement of the mass of a molecule. Structural information may be gleaned by fragmenting the molecule and measuring the masses of its constituent parts. Dissociation of a molecule followed by mass measurement of the fragments is known as tandem mass spectrometry. Several established techniques exist for inducing fragmentation however each has limitations, such as the inability to cleave certain chemical bonds.Electron capture dissociation (ECD) is a recently developed tandem mass spectrometry technique which shows a number of advantages for the structural analysis of peptides and proteins. However, the mechanism by which ECD occurs is not clearly defined and we cannot be certain that we are realising the potential of this analytical technique. Furthermore, the ECD of other molecular structures has not been comprehensively addressed.The proposed work will address ECD as an analytical technique in a broader context than previous investigations. We will define the ECD behaviour of particular peptides, polymers and fullerenes. The main outcome will be a better understanding of the mechanisms of ECD. As a result, it will be possible to optimise ECD performance and gain maximum structural information for a variety of molecular structures.

Publications

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Jones AW (2010) Electron capture dissociation mass spectrometry of tyrosine nitrated peptides. in Journal of the American Society for Mass Spectrometry

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Jones AW (2012) The radical ion chemistry of S-nitrosylated peptides. in Journal of the American Society for Mass Spectrometry

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Jones AW (2010) Probing the mechanisms of ECD mass spectrometry with nitrated peptides in Physical Chemistry, Chemical Physics

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Kaczorowska MA (2013) Electron capture dissociation and collision induced dissociation of S-dipalmitoylated peptides. in Journal of the American Society for Mass Spectrometry

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Kaczorowska MA (2009) Characterization of polyphosphoesters by Fourier transform ion cyclotron resonance mass spectrometry. in Journal of the American Society for Mass Spectrometry

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Kaczorowska MA (2010) Electron capture dissociation mass spectrometry of metallo-supramolecular complexes. in Journal of the American Society for Mass Spectrometry

 
Description Prior to this work, it was well-established that electron capture dissociation (ECD) mass spectrometry offers a number of advantages for the analysis of peptides and proteins. However, a complete fundamental understanding of the processes that occur following electron capture by these species was lacking. Moreover, the ECD behaviours of other molecular structures had been neglected. The aim here was to investigate the fundamental mechanisms of ECD in order that its potentials are identified and realised. The project was broken down into a number of research objectives:



1. To investigate the effect of nitration and S-bonded modifications on peptide ECD.

Sulfur-bonded modifications play an important role in biology and are necessary for the function of many proteins. On the other hand, nitration of proteins is a biomarker of disease. In both cases, there is a need to be able to characterise the modifications. Our work showed that for nitration, ECD was not the method of choice, however our results provided enormous insight into the hierarchy of mechanisms of ECD and resulted in two highly-cited publications. A number of S-modifications were considered, including S-nitrosylation, oxidation, and alkylation. Further insight into the mechanisms of ECD were gained, and a paper on S-nitrosylation was published.



2. To determine the ECD behaviour of polyesters and polyphosphoesters.

The ECD of polyesters was similar to that obtained for other polymers PEG and PPG. ECD and an alternative technique, collision-induced dissociation, was applied to a polyphosphoester and its degradation products. The pathways by which the polymer was hydrolysed were elucidated. The work was published in the Journal of the American Society for Mass Spectrometry.



3. To determine the ECD behaviour of dendrimers.

Dendrimers are highly branched polymers which have discreet molecular weights. The aim was to determine whether ECD could provide structural information about the individual components of the dendrimer and what effect does the end group have on ECD behaviour. The work showed that ECD was suitable for dendrimer analysis, and provided insight into the mechanisms of ECD, particularly with regard to the effect of metal adduction. This work produced two publications.



4. The success of the previous research objective led us to investigate the ECD of other metal containing species. The ECD of metallo (Fe)-supramolecular dinuclear triple-stranded helicates was determined and compared with that obtained for Ag and Cu double stranded complexes. The results suggested that ECD by metallo-complexes allows access, in the gas-phase, to oxidation states and coordination that cannot be accessed in solution. This work was published in the Journal of the American Society for Mass Spectrometry.



5. The latter finding was further explored. ECD is limited to multiply-charged cations. However, we investigated an alternative approach in which singly-charged species are irradiated with higher energy electrons, termed electron-induced dissociation (EID). This was applied to oxo-centred trinuclear carboxylate-bridged iron complexes, and compared with CID. The work showed that EID was a particularly useful structural elucidation tool for these species. This work was published in the Journal of the American Society for Mass Spectrometry.
Exploitation Route The work on peptides will find use in the field of proteomics, while the work on polyphosphoesters will find use in the characterisation of polymers. Electron induced dissociation mass spectrometry is an emerging field in analytical chemistry. It is showing great potential for the structural characterisation of molecular species which will only form singly-charged species in the gas-phase.
Sectors Chemicals,Pharmaceuticals and Medical Biotechnology

 
Description The findings have provided a fundamental understanding of the gas phase radical ion chemistry of a range of molecular classes. To date, the findings have been used within academia. Ten papers were published as a result of this work and these have been cited 104 times (as of 08 Nov 2014).
First Year Of Impact 2008
Sector Chemicals