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Protein identification and characterization through peptide mass spectrometry

method development for improved ricin and botulinum neurotoxin analysis

Bergström, Tomas (2016). Protein identification and characterization through peptide mass spectrometry. Diss. (sammanfattning/summary) Umeå : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2016:99
ISBN 978-91-576-8700-5
eISBN 978-91-576-8701-2
[Doctoral thesis]

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Abstract

The illicit usage of toxic substances is increasing rapidly around the world, creating a need for comprehensive chemical methods for detecting and quantitating toxic agents that might be used in criminal activities or terror attacks. There are several toxic proteins that could potentially be used in bioterrorism or biocrime. For example, the plant toxins ricin and abrin are readily available, very toxic, and easily produced, and are therefore frequently involved in biocrime incidents. Another threat agent is the extremely poisonous botulinum neurotoxin, which is among the most toxic substances known. Forensic analyses of samples potentially containing these diverse and very toxic agents therefore require analytical methods capable of detecting trace amounts of the target analyte in complex mixtures.

This thesis describes the development of new methods for peptide mass spectrometry that offer improved performance in forensic toxin analysis. A galactose affinity method was developed for the enrichment and subsequent analysis of ricin, abrin and botulinum neurotoxin. The method’s applicability was confirmed during a forensic investigation into illegal toxin preparations. Additionally, the investigations generated new information on the structural properties of ricin that will facilitate the forensic matching of samples to sources. Details of botulinum neurotoxin’s sophisticated intoxication mechanisms were determined by using a broad analytical approach to study the importance and heterogeneity of SV2C glycosylation.

Overall, the results and procedures presented in this thesis will help to improve analytical capabilities relevant to the detection and prevention of biocrime and bioterrorism. More generally, it provides methodological guidance and useful strategies for researchers in peptide mass spectrometry.

Authors/Creators:Bergström, Tomas
Title:Protein identification and characterization through peptide mass spectrometry
Subtitle:method development for improved ricin and botulinum neurotoxin analysis
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :2016
Depositing date:20 September 2016
Volume:2016:99
Number of Pages:69
Papers/manuscripts:
NumberReferences
IBergström T, Fredriksson S-Å, Nilsson C, Åstot C (2015). Deamidation in ricin studied by capillary zone electrophoresis- and liquid chromatography-mass spectrometry. Journal of Chromatography B 974, 109–117.
IIFredriksson S-Å, Artursson E, Bergström T, Östin A, Nilsson C, Åstot C (2015). Identification of RIP-II toxins by affinity enrichment, enzymatic digestion and LC-MS. Analytical Chemistry 87(2), 967-74.
IIIBergström T, Fredriksson S-Å, and Åstot C. Selective botulinum neurotoxin enrichment based on progenitor complex chemistry followed by LC-MS identification. Manuscript.
IVMahrhold S, Bergström T, Stern D, Dorner BG, Åstot C, Rummel A (2016). Only the complex N559-glycan in synaptic vesicle glycoprotein 2C mediates high affinity binding to botulinum neurotoxin serotype A1. Biochemical Journal 473(17), 2645-2654.
Place of Publication:Umeå
Publisher:Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-576-8700-5
ISBN for electronic version:978-91-576-8701-2
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:Q Food science > Q03 Food contamination and toxicology
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 104 Chemical Sciences > Analytical Chemistry
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Neurosciences
Agrovoc terms:mass spectrometry, neurotoxins, ricin, clostridium botulinum, poisoning, proteins, peptides, analytical methods, delinquent behaviour, illegal practices
Keywords:biocrime, bioterrorism, mass spectrometry, toxin, Ricinus communis, ricin, abrin, botulinum neurotoxin, Clostridium botulinum, deamidation
URN:NBN:urn:nbn:se:slu:epsilon-e-3677
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-3677
ID Code:13672
Faculty:S - Faculty of Forest Sciences
Department:(S) > Dept. of Forest Genetics and Plant Physiology
External funders:Myndigheten för samhällsskydd och beredskap / Swedish Civil Contingencies Agency
Deposited By: Tomas Bergström
Deposited On:21 Sep 2016 08:58
Metadata Last Modified:21 Sep 2016 09:09

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