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Synthesis of ganglioside and lysoganglioside lipoforms as internal standards for MS quantification

dc.contributor.advisorKolter, Thomas
dc.contributor.authorGantner, Martin
dc.date.accessioned2020-04-20T19:01:14Z
dc.date.available2020-04-20T19:01:14Z
dc.date.issued08.01.2015
dc.identifier.urihttp://hdl.handle.net/20.500.11811/6394
dc.description.abstractThe goal of this work was to establish methods for the synthesis of modified gangliosides that are suitable as internal standards for mass spectrometry. Quantification of gangliosides is usually achieved by staining after chromatographic separation, most often by thin layer chromatography and subsequent densitometric analysis. These procedures are usually not suitable for the determination of different lipoforms of a given ganglioside. Within the recent years, ganglioside patterns have been increasingly analyzed by mass spectrometry due to the high sensitivity and specificity of this method. Due to the lack of suitable standard substances for internal calibration, MS gives no reliable information on the amount of complex gangliosides in samples of biological origin: Standard substances are only available for gangliosides GM1, GM2, and GM3. During this work structural analogs of the brain gangliosides GM1, GD1a, GD1b, GT1b, and GQ1b have been prepared from mixtures of bovine brain gangliosides. Also standard substances for the tumor-associated gangliosides GM2 and GD2 have been prepared. They are important targets for immunotherapy because they are highly expressed on human tumors of neuroectodermal origin while they are only minor gangliosides in healthy tissue. Furthermore, the quantification of GM2 is of interest in lysosomal storage diseases. In addition, a method based on an olefin metathesis has been established that is suitable for the synthesis of modified lysogangliosides. By this, non-natural lipoforms have been prepared that are suitable as internal standards for lyso-GM1 and lyso-GM2. These substances are potential biomarkers for GM1-gangliosidosis and GM2-gangliosidoses and the lysoganglioside standards prepared in this work can be used for their quantification. Currently, the standard substances are applied for the analysis of the brains of genetically engineered mice with deficiency of ceramide synthase 4.
dc.language.isoeng
dc.rightsIn Copyright
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectInterner Standard
dc.subjectGlycolipide
dc.subjectSphingolipide
dc.subjectMassenspektrometrie
dc.subjectOlefinmetathese
dc.subjectInternal standard
dc.subjectglycolipids
dc.subjectsphingolipids
dc.subjectmass spectrometry
dc.subjectolefin metathesis
dc.subject.ddc540 Chemie
dc.subject.ddc570 Biowissenschaften, Biologie
dc.subject.ddc610 Medizin, Gesundheit
dc.titleSynthesis of ganglioside and lysoganglioside lipoforms as internal standards for MS quantification
dc.typeDissertation oder Habilitation
dc.publisher.nameUniversitäts- und Landesbibliothek Bonn
dc.publisher.locationBonn
dc.rights.accessRightsopenAccess
dc.identifier.urnhttps://nbn-resolving.org/urn:nbn:de:hbz:5n-38756
ulbbn.pubtypeErstveröffentlichung
ulbbnediss.affiliation.nameRheinische Friedrich-Wilhelms-Universität Bonn
ulbbnediss.affiliation.locationBonn
ulbbnediss.thesis.levelDissertation
ulbbnediss.dissID3875
ulbbnediss.date.accepted2014-12-10
ulbbnediss.instituteMathematisch-Naturwissenschaftliche Fakultät : Fachgruppe Molekulare Biomedizin / Life & Medical Sciences-Institut (LIMES)
ulbbnediss.fakultaetMathematisch-Naturwissenschaftliche Fakultät
dc.contributor.coRefereeMenche, Dirk


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