Comparison of CID spectra of singly charged polypeptide antibiotic precursor ions obtained by positive‐ion vacuum MALDI IT/RTOF and TOF/RTOF, AP‐MALDI‐IT and ESI‐IT mass spectrometry

Pittenauer, Ernst; Zehl, Martin; Belgacem, Omar; Raptakis, E.; Mistrik, Robert; Allmaier, Günter

doi:10.1002/jms.1032

Cited by 44 publications

(38 citation statements)

References 41 publications

(23 reference statements)

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“…This may account for the difference in mass of ϳ0.2 Da observed and may therefore explain the poor fragmentation behavior found by CID. This data strongly indicates that CHO TGase activity is to some extent distinct from guinea pig TGase, by showing strong preference for intramolecular cross-linking hence resulting in a structural rearrangement, similar to earlier reported peptide cyclization found in polypeptide antibiotics (35). This putative structural difference will be the subject of our future studies, using electron transfer dissociation combined with CID fragmentation to elucidate any intramolecular rearrangement following cross-linking with different TGase isoforms.…”

Section: Investigation Of Endogenous Tgase Cross-linking Activity In supporting

confidence: 82%

Tissue Transglutaminase-mediated Glutamine Deamidation of β-Amyloid Peptide Increases Peptide Solubility, Whereas Enzymatic Cross-linking and Peptide Fragmentation May Serve as Molecular Triggers for Rapid Peptide Aggregation

Schmid

Condemi

Tuchscherer

et al. 2011

Journal of Biological Chemistry

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Tissue transglutaminase (TGase) has been implicated in a number of cellular processes and disease states, where the enzymatic actions of TGase may serve in both, cell survival and apoptosis. To date, the precise functional properties of TGase in cell survival or cell death mechanisms still remain elusive. TGasemediated cross-linking has been reported to account for the formation of insoluble lesions in conformational diseases. We report here that TGase induces intramolecular cross-linking of ␤-amyloid peptide (A␤), resulting in structural changes of monomeric A␤. Using high resolution mass spectrometry (MS) of cross-linked A␤ peptides, we observed a shift in mass, which is, presumably associated with the loss of NH 3 due to enzymatic transamidation activity and hence intramolecular peptide cross-linking. We have observed that a large population of A␤ monomers contained an 0.984 Da increase in mass at a glutamine residue, indicating that glutamine 15 serves as an indispensable substrate in TGase-mediated deamidation to glutamate 15. We provide strong analytical evidence on TGasemediated A␤ peptide dimerization, through covalent intermolecular cross-linking and hence the formation of A␤ 1-40 dimers. Our in depth analyses indicate that TGase-induced post-translational modifications of A␤ peptide may serve as an important seed for aggregation.

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Section: Investigation Of Endogenous Tgase Cross-linking Activity In supporting

confidence: 82%

Tissue Transglutaminase-mediated Glutamine Deamidation of β-Amyloid Peptide Increases Peptide Solubility, Whereas Enzymatic Cross-linking and Peptide Fragmentation May Serve as Molecular Triggers for Rapid Peptide Aggregation

Schmid

Condemi

Tuchscherer

et al. 2011

Journal of Biological Chemistry

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“…The digests were desalted and concentrated using ZipTips (C 18 , Millipore, Bedford, MA) and analyzed on a MALDI-TOF/reflectron TOF instrument (TOF 2 (11,12); Shimadzu Biotech, Manchester, UK) applying the thin layer preparation technique (13) using ␣-cyano-4-hydroxycinnamic acid (Sigma-Aldrich) as matrix. All mass spectra were recorded in positive ion reflectron mode with delayed extraction by accumulating up to 500 single unselected laser shots.…”

mentioning

confidence: 99%

Biological Variation of the Platelet Proteome in the Elderly Population and Its Implication for Biomarker Research

Winkler

Zellner

Diestinger

et al. 2008

Molecular & Cellular Proteomics

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Knowledge about the extent of total variation experienced between samples from different individuals is of great importance for the design of not only proteomics but every clinical study. This variation defines the smallest statistically significant detectable signal difference when comparing two groups of individuals. We isolated platelets from 20 healthy human volunteers aged 56 -100 years because this age group is most commonly encountered in the clinics. We determined the technical and total variation experienced in a proteome analysis using two-dimensional DIGE with IPGs in the pI ranges 4 -7 and 6 -9. Only spots that were reproducibly detectable in at least 90% of all gels (n ‫؍‬ 908) were included in the study. All spots had a similar technical variation with a median coefficient of variation (cv) of about 7%. In contrast, spots showed a more diverse total variation between individuals with a surprisingly low median cv of only 18%. Because most known biomarkers show an effect size in a 1-2-fold range of their cv, any future clinical proteomics study with platelets will require an analytical method that is able to detect such small quantitative differences. In addition, we calculated the minimal number of samples (sample size) needed to detect given protein expression differences with statistical significance. Molecular & Cellular Proteomics 7:193-203, 2008.Biomarkers are used to differentiate between different biological states and to monitor disease progress or the success of medical treatment. To fulfill these tasks, there are not only strict requirements for each biomarker candidate in terms of selectivity and specificity but also for the precision of the analytical process. Therefore knowledge on the extent of variation between the individuals within each group is crucial for the study design as well as the selection of the method of measurement. The total variation experienced between individuals within one group is the result of the biological variation caused by factors like sex, age, genetic background, lifestyle, or health status and the technical variation introduced by the applied sample handling and the method of measurement itself. This study investigated the extent of variation in human blood platelets. Platelets are responsible for the maintenance of vascular integrity and are also involved in inflammation and wound healing (1). They are anucleate cytoplasmic fragments released from megakaryocytes in the bone marrow. During platelet biogenesis, organelles, especially the mitochondria and the ␣-and dense granules, are actively transported into the platelets. Furthermore platelets receive a certain set of mRNAs during their biogenesis from the megakaryocytes and are still capable of protein synthesis and processing (2). Several proteomics studies have focused on different aspects in platelet research using 2D 1 electrophoresis followed by mass spectrometry. These studies provided 2D maps of the total platelet proteome (3, 4), the platelet secretome (5), and the processes during platelet activ...

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“…[20] In einem weiteren Ansatz wurden sämtliche Amid-Wasserstoffatome durch Deuterium substituiert, wobei alle ND-Streckschwingungen auf Werte unter 2500 cm À1 verschoben werden, sodass für eine erleichterte Bandenzuordnung nur die CH-Streckschwingungen in der Region von 3 mm verbleiben (Abbildung 1 b). Das Verschieben der ND-Beugungsschwingungen hin zu niedrigeren [7] und Infrarot-Multiphotonendissoziation (IRMPD; Abbildung H1) vernachlässigbar sind. Die beobachtete nicht-statistische Dissoziation [26] lässt einen anfängli-chen Transfer von Photoanregungsenergie direkt von den Phe-Chromophoren auf die Amine der Orn-Seitenketten vermuten und impliziert eine gewisse Nähe und Kopplung zwischen den beiden Gruppen.…”

Section: Methodsunclassified

Kalte Ionenspektroskopie zur Lösung der Gasphasenstruktur eines Decapeptids

et al. 2011

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Gefangen, gekühlt, gelöst: Die Gasphasenstruktur des natürlichen Decapeptids Gramicidin S wurde durch kalte Ionenspektroskopie aufgeklärt. Die Messungen liefern einen Satz von spektroskopischen und Struktureigenschaften, die die stabilste berechnete Struktur des isolierten Peptids eindeutig bestätigen (siehe Bild). Die Strukturdaten können zur Modellierung der biologischen Aktivität des Antibiotikums genutzt werden.

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Comparison of CID spectra of singly charged polypeptide antibiotic precursor ions obtained by positive‐ion vacuum MALDI IT/RTOF and TOF/RTOF, AP‐MALDI‐IT and ESI‐IT mass spectrometry

Cited by 44 publications

References 41 publications

Tissue Transglutaminase-mediated Glutamine Deamidation of β-Amyloid Peptide Increases Peptide Solubility, Whereas Enzymatic Cross-linking and Peptide Fragmentation May Serve as Molecular Triggers for Rapid Peptide Aggregation

Tissue Transglutaminase-mediated Glutamine Deamidation of β-Amyloid Peptide Increases Peptide Solubility, Whereas Enzymatic Cross-linking and Peptide Fragmentation May Serve as Molecular Triggers for Rapid Peptide Aggregation

Biological Variation of the Platelet Proteome in the Elderly Population and Its Implication for Biomarker Research

Kalte Ionenspektroskopie zur Lösung der Gasphasenstruktur eines Decapeptids

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