Ph.D. Student, Analytical Chemistry, FT-ICR MS

Analysis of homopolymers, copolymers, and peptide-polymer conjugates by FT-ICR

Tomos is now a post-doc working on the development of antibody mass spectrometry methods in a collaboration with thermofisher and NIBRT (Dublin). He can be contacted on: tomos.morgan@nibrt.ie

Accurate characterisation of biocompatible polymers, cyclic peptides, and cyclic peptide-polymer conjugates is of great use to research and development scientists in all forms of pharmaceutical and biopharmaceutical industry. The project generated a number of positive research outcomes:

Electron Capture Dissociation of polyoxazolines

The Paper "Coupling Electron Capture Dissociation and the modified Kendrick mass defect for sequencing of a poly(2-ethyl-2-oxazoline) polymer" showed how ECD offers a structurally robust method for the analysis of polyoxazolines. The coupling of modified Kendrick mass defect (Kendrick analysis, fractional Kendrick mass) to the fragmentation analysis was greatly beneficial to the rapid assignment of spectra. Read Thierry Fouquet's papers for in depth discussion on Kendrick analysis for polymers: https://scholar.google.lu/citations?user=NAkooqIAAAAJ&hl=en.

New insights into Electron capture dissocaition: Fragmentation of polyacrylamides

The Paper "Electron Capture Dissociation of trithiocarbonate-terminated acrylamide homo- and co-polymers: A terminus directed mechanism?" showed how a completely novel dissociation mechanism with electron capture occurring at the polymer terminus and free radical cascade down the polymer chain causing fragmentation. The study used double resonance in the FT-ICR to show how fragmentation was occurring, (a pretty retro technique!)

Analysis of random copolymers: hydrolysed polyoxazolines

The use of mass spectrometry to better characterise random copolymers was shown to be a highly effective method of analysis. If the randomness of the hydrolysis is treated as a permutation through a polymer backbone a modified Heap's algorithm can be used for analysis.

UVPD analysis of cyclic-peptide polymer conjugates

UVPD offers a two-birds one-stone approach to analysis of cyclic-peptide polymer conjugate, being able to characterise the cyclic peptide and the polymer through one dissocaition method.

Accurate determination and analysis of polymers and peptide-polymer conjugates is seeing greater interest as these species see greater clinical use. Accurate quantitation of peptides and proteins using fragmentation methods via FT-ICR MS is well established and investigation of these methods as a part of polymer and peptide-polymer conjugate analysis is gaining interest.

Analysis of complex polymer ESI spectra can be carried out by effectively coupling ultrahigh resolution mass spectrometry data with powerful data analysis polymer properties can be established quickly.

Fragmentation of polymers as a way to understand sequence and end group information is important for better understanding these conjugated agents. As part of this work, polyoxazoline and polyacrylamide fragmentation has been carried out and better understood.

Two-dimensional mass spectrometry methods are also seeing increased use with fragmentation analysis of cyclic peptide polymer conjugates being carried out. This work is being developed by the O'Connor group as a new way to handle MS/MS data. This work is data heavy so novel data handling methods are developed and utilised within the O'Connor group as a way to process the dense data sets produced.

Publications

Tomos E. Morgan, Sean H. Ellacott, Christopher A. Wootton, Mark P. Barrow, Anthony W. T. Bristow, Sebastien Perrier, Peter B. O'Connor, Coupling Electron Capture Dissociation and the modified Kendrick mass defect for sequencing of a poly(2-ethyl-2-oxazoline) polymer., Anal. Chem., 2018, 90 (19) 11710-11715. https://pubs.acs.org/doi/10.1021/acs.analchem.8b03591

Johanna Paris, Tomos E. Morgan, Christopher A. Wootton, Mark P. Barrow, John O'Hara, Peter B. O'Connor, Facile determination of phosphorylation sites in peptides using 2DMS, Anal. Chem., Just Accepted Manuscript. https://pubs.acs.org/doi/abs/10.1021/acs.analchem.0c00884

Bryan P. Marzullo, Tomos E. Morgan, Christopher A. Wootton, Meng Li, Simon J. Perry, Mansoor Saeed, Mark P. Barrow, Peter B. O'Connor, Comparison of Fragmentation Techniques for the structural characterisation of singly charged agrochemicals, Anal. Chem., 2020, 92, 4, 3143-3151.

Maria A. van Agthoven, David P. A. Kilgour, Alice M. Lynch, Mark P. Barrow, Tomos E. Morgan, Christopher A. Wootton, Lionel Chiron, Marc-Andre Delsuc, Peter B. O'Connor, Journal of The American Society for Mass Spectrometry, 2019, 30, 12, 2594-2607.

Maria A. van Agthoven, Alice M. Lynch, Tomos E. Morgan, Christopher A. Wootton, Yuko P. Y. Lam, Lionel Chiron, Mark P. Barrow, Marc-Andre Delsuc, Peter B. O'Connor, Can Two-Dimensional IR-ECD Mass Spectrometry Improve Peptide de Novo Sequencing?, Anal. Chem., 2018, 90, 3496. DOI:10.1021/acs.analchem.7b05324, https://pubs.acs.org/doi/pdf/10.1021/acs.analchem.7b05324

Oral and poster presentations

Modifying the Kendrick Mass Defect for polymer analysis, (oral, EFTMS: Young speaker prize winner) Tomos E. Morgan, Christopher A. Wootton, Andrew Kerr, Sean Ellacott, Rémy Gavard, Diana Catalina Palacio, Maria A. van Agthoven, Mark P. Barrow, Anthony W. T. Bristow, Sebastien Perrier, Peter B. O’Connor

Advancing biocompatible synthetic polymer mass spectrometry into the second dimension, (oral, Warwick postgraduate symposium: best analytical talk prize winner) Tomos E. Morgan, Christopher A. Wootton, Andrew Kerr, Sean Ellacott, Rémy Gavard, Diana Catalina Palacio, Maria A. van Agthoven, Mark P. Barrow, Anthony W. T. Bristow, Sebastien Perrier, Peter B. O’Connor

2D-MS ECD of polyoxazolines, (oral, UPCONN) Tomos E. Morgan, Christopher A. Wootton, Sean Ellacott, Maria A. van Agthoven, Mark P. Barrow, Anthony W. T. Bristow, Sebastien Perrier, Peter B. O’Connor

Analysis of polyoxazolines by 2D-MS, (Poster, BMSS 2018) Tomos E. Morgan, Christopher A. Wootton, Sean Ellacott, Maria A. van Agthoven, Mark P. Barrow, Anthony W. T. Bristow, Sebastien Perrier, Peter B. O’Connor

Cyclic peptide-polymer conjugate characterisation using SNAP algorithm and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry, (Poster, BMSS 2017) Tomos E. Morgan*, Christopher A. Wootton, Sebastien Perrier, Anthony W. T. Bristow, Mark P. Barrow and Peter B. O’Connor

Analysis of polymers by ultra-high resolution FT-ICR MS, (oral, Polymer club) Tomos E. Morgan*, Christopher A. Wootton, Sebastien Perrier, Anthony W. T. Bristow, Mark P. Barrow and Peter B. O’Connor

Conferences

Warwick Postgraduate symposium, University of Warwick, May 2019.

Celebration in Native Mass Spectrometry, Oxford, Mar 2019.

British Mass Spectrometry Society Conference (BMSS), Manchester, Sep 2018.

UpCONN, Leeds, Jul 2018.

European Fourier Transform Mass Spectrometry Conference (EFTMS), Freising, Munich, Apr 2018

British Mass Spectrometry Society Conference (BMSS), Manchester, Sep 2017.

Analytical Research Forum, Burlington House, London, Jul 2017.

Polymer Club conference, University of Warwick, May 2016.

Polymer Club conference, University of Warwick, Nov 2016.

Personal Profile

Tomos carried out an integrated Master's degree in chemistry (MChem) at the University of East Anglia. As part of his studies, he carried out a year in industry with GlaxoSmithKline working in Quality Assurance, the majority of this time was spent working on HPLC systems and method transfer between analytical development and manufacturing. Before this, he spent two summers working for Genzyme, now a Sanofi company, in Process Analytical Technology working with Raman techniques for analysis of bioreactor products and Mass Spectrometry for analysis of oligonucleotides. As part of his final Master's project Tomos carried out the synthesis of gold(III) organometallic complexes, this synthesis was carried out in air-sensitive conditions and involved IR, NMR, and UV analysis.

Tomos E. Morgan
Analytical Chemistry PhD student (FT-ICR MS)
CASE Student in partnership with AstraZeneca
email: t.morgan.3@warwick.ac.uk

orcid.org/0000-0002-3366-8889

Scholar: https://scholar.google.com/citations?user=Mysl3l4AAAAJ&hl=en