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Ion Mobility- Mass Spectrometry and Affinity- Mass Spectrometry : New Tools for elucidation of structures and reaction pathways of "misfolding" - aggregating neurodegenerative proteins

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Ion Mobility- Mass Spectrometry and Affinity- Mass Spectrometry : New Tools for elucidation of structures and reaction pathways of "misfolding" - aggregating neurodegenerative proteins

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PRZYBYLSKI, Michael, Kathrin LINDNER, Camelia VLAD, Marilena MANEA, Nicholas A. PIERSON, I. STRUBE, Christiaan KARREMAN, Stefan SCHILDKNECHT, Marcel LEIST, John RONTREE, 2012. Ion Mobility- Mass Spectrometry and Affinity- Mass Spectrometry : New Tools for elucidation of structures and reaction pathways of "misfolding" - aggregating neurodegenerative proteins. In: Journal of Peptide Science. Wiley. 18(S1), pp. S22. ISSN 1075-2617. eISSN 1099-1387. Available under: doi: 10.1002/psc.2446

@article{Przybylski2012Mobil-52628, title={Ion Mobility- Mass Spectrometry and Affinity- Mass Spectrometry : New Tools for elucidation of structures and reaction pathways of "misfolding" - aggregating neurodegenerative proteins}, year={2012}, doi={10.1002/psc.2446}, number={S1}, volume={18}, issn={1075-2617}, journal={Journal of Peptide Science}, author={Przybylski, Michael and Lindner, Kathrin and Vlad, Camelia and Manea, Marilena and Pierson, Nicholas A. and Strube, I. and Karreman, Christiaan and Schildknecht, Stefan and Leist, Marcel and Rontree, John}, note={Meeting Abstract Article Number: Meeting Abstract} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/52628"> <dc:contributor>Strube, I.</dc:contributor> <dc:creator>Manea, Marilena</dc:creator> <dc:contributor>Rontree, John</dc:contributor> <dc:creator>Pierson, Nicholas A.</dc:creator> <dc:creator>Leist, Marcel</dc:creator> <dc:contributor>Vlad, Camelia</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-01-29T12:21:29Z</dc:date> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:rights>terms-of-use</dc:rights> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-01-29T12:21:29Z</dcterms:available> <dcterms:issued>2012</dcterms:issued> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/52628"/> <dc:contributor>Schildknecht, Stefan</dc:contributor> <dcterms:abstract xml:lang="eng">A large variety of cellular processes are based on the formation and dynamics of multi- and supramolecular protein assemblies, and several diseases, previously thought to be unrelated, such as cancer and neurodegenerative diseases, are characterised by “misfolded” protein aggregates. Chemical structures and reaction pathways of pathophysiological aggregates are only poorly characterised and understood at present. “Softionisation” mass spectrometry (MS), such as HPLC-electrospray-MS, is often unsuitable to direct analysis of reaction pathways and intermediates in aggregation. Recently, ion mobility- MS (IM-MS) has been emerging as a new tool for analysis of protein aggregates due to its concentration-independent gas phase separation capability. First applications of IM-MS to in vitro oligomerization products of α-synuclein (αSyn) and ß amyloid key proteins for Parkinson’s disease and Alzheimer’s disease, enabled hitherto unknown truncation and aggregation products to be identified. Studies of the in vitro oligomerization- aggregation of αSyn provided the first identification of specific autoproteolytic fragments, previously observed by gel electrophoresis but not identified [1]. A highly aggregating fragment found by cleavage at V71- T72 in the central aggregation domain of αSyn, αSyn(72-140), was prepared by chemical synthesis and recombinant expression and showed substantially faster oligomerization- aggregation, and higher neurotoxicity compared to the intact protein. Recently, the development and application of combined (online) affinity- MS methods enabled the structural identification of epitope-specific Aß-antibodies that disaggregate Aßplaques, and physiological neuroprotective Aß-autoantibodies inhibiting the formation of Aßaggregates. These results indicate ion mobility- MS and affinity- MS as powerful tools for the molecular elucidation of structures and intermediates of polypeptide aggregates. The structures thus obtained provide a basis for (i), the detailed study of oligomerization- aggregation pathways; (ii), the design of peptides capable of inhibiting or modifying aggregation; and (iii), the evaluation of new immunotherapeutic lead structures.</dcterms:abstract> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Lindner, Kathrin</dc:contributor> <dcterms:title>Ion Mobility- Mass Spectrometry and Affinity- Mass Spectrometry : New Tools for elucidation of structures and reaction pathways of "misfolding" - aggregating neurodegenerative proteins</dcterms:title> <dc:creator>Lindner, Kathrin</dc:creator> <dc:creator>Rontree, John</dc:creator> <dc:contributor>Pierson, Nicholas A.</dc:contributor> <dc:creator>Strube, I.</dc:creator> <dc:contributor>Przybylski, Michael</dc:contributor> <dc:creator>Przybylski, Michael</dc:creator> <dc:creator>Karreman, Christiaan</dc:creator> <dc:contributor>Manea, Marilena</dc:contributor> <dc:language>eng</dc:language> <dc:creator>Vlad, Camelia</dc:creator> <dc:contributor>Karreman, Christiaan</dc:contributor> <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/> <dc:contributor>Leist, Marcel</dc:contributor> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:creator>Schildknecht, Stefan</dc:creator> </rdf:Description> </rdf:RDF>

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