ORCID Profile
0000-0001-8054-4718
Current Organisation
Freie Universität Berlin
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Publisher: Wiley
Date: 02-03-2020
Publisher: Wiley
Date: 24-03-2022
Abstract: Over the course of the COVID-19 pandemic, mRNA-based vaccines have gained tremendous importance. The development and analysis of modified RNA molecules benefit from advanced mass spectrometry and require sufficient understanding of fragmentation processes. Analogous to the degradation of RNA in solution by autohydrolysis, backbone cleavage of RNA strands was equally observed in the gas phase however, the fragmentation mechanism remained elusive. In this work, autohydrolysis-like intermediates were generated from isolated RNA dinucleotides in the gas phase and investigated using cryogenic infrared spectroscopy in helium nanodroplets. Data from both experiment and density functional theory provide evidence for the formation of a five-membered cyclic phosphate intermediate and rule out linear or six-membered structures. Furthermore, the experiments show that another prominent condensed-phase reaction of RNA nucleotides can be induced in the gas phase: the tautomerization of cytosine. Both observed reactions are therefore highly universal and intrinsic properties of the investigated molecules.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0AN00433B
Abstract: In analogy to chromatography, a plate-height model of drift tube ion mobility-mass spectrometry is presented that describes zone broadening and resolving power in ion mobility separations.
Publisher: Springer Science and Business Media LLC
Date: 11-02-2022
DOI: 10.1007/S00216-022-03927-6
Abstract: Tandem mass spectrometry is arguably the most important analytical tool for structure elucidation of lipids and other metabolites. By fragmenting intact lipid ions, valuable structural information such as the lipid class and fatty acyl composition are readily obtainable. The information content of a fragment spectrum can often be increased by the addition of metal cations. In particular, the use of silver ions is deeply rooted in the history of lipidomics due to their propensity to coordinate both electron-rich heteroatoms and C = C bonds in aliphatic chains. Not surprisingly, coordination of silver ions was found to enable the distinction of sn -isomers in glycerolipids by inducing reproducible intensity differences in the fragment spectra, which could, however, not be rationalized. Here, we investigate the fragmentation behaviors of silver-adducted sn - and double bond glycerophospholipid isomers by probing fragment structures using cryogenic gas-phase infrared (IR) spectroscopy. Our results confirm that neutral headgroup loss from silver-adducted glycerophospholipids leads to dioxolane-type fragments generated by intramolecular cyclization. By combining high-resolution IR spectroscopy and computational modelling of silver-adducted fragments, we offer qualitative explanations for different fragmentation behaviors of glycerophospholipid isomers. Overall, the results demonstrate that gas-phase IR spectroscopy of fragment ions can significantly contribute to our understanding of lipid dissociation mechanisms and the influence of coordinating cations. Graphical abstract
Publisher: Springer Science and Business Media LLC
Date: 22-02-2021
DOI: 10.1038/S41467-021-21480-1
Abstract: Glycolipids are complex glycoconjugates composed of a glycan headgroup and a lipid moiety. Their modular biosynthesis creates a vast amount of erse and often isomeric structures, which fulfill highly specific biological functions. To date, no gold-standard analytical technique can provide a comprehensive structural elucidation of complex glycolipids, and insufficient tools for isomer distinction can lead to wrong assignments. Herein we use cryogenic gas-phase infrared spectroscopy to systematically investigate different kinds of isomerism in immunologically relevant glycolipids. We show that all structural features, including isomeric glycan headgroups, anomeric configurations and different lipid moieties, can be unambiguously resolved by diagnostic spectroscopic fingerprints in a narrow spectral range. The results allow for the characterization of isomeric glycolipid mixtures and biological applications.
Publisher: Wiley
Date: 30-07-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3CP03776B
Abstract: In past decades, hydrogen bonds involving organic fluorine have been a highly disputed topic. Obtaining clear evidence for the presence of fluorine-specific interactions is generally difficult because of their weak...
Publisher: Wiley
Date: 18-05-2020
Publisher: Wiley
Date: 24-04-2022
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-12-2021
Abstract: This study provides proof of concept for cell-based heparin without heparin-induced thrombocytopenia side effects.
Publisher: Wiley
Date: 05-05-2023
Abstract: Fucose ist ein signalgebendes Kohlenhydrat, das am Ende der Glykosylierung angehängt wird. Es ist an einer Reihe von Prozessen beteiligt, z. B. an der Selectin‐abhängigen Leukozytenadhäsion oder an Pathogen‐Rezeptor‐Interaktionen. Massenspektrometrische Verfahren, die üblicherweise zur Bestimmung der Struktur von Glykanen eingesetzt werden, zeigen häufig Fucose‐haltige, chimäre Fragmente, die die Analyse verzerren. Die Umlagerung, die zu diesen Fragmenten führt – oft als Fucose‐Migration bezeichnet – ist seit mehr als 25 Jahren bekannt, aber die chemische Identität des Umlagerungsproduktes bleibt unklar. In dieser Arbeit kombinieren wir Ionenmobilitätsspektrometrie, Massenspektrometrie mit radikalinduzierter Dissoziation, kryogene IR‐Spektroskopie und Computersimulationen mittels Dichtefunktionaltheorie, um das Produkt der Umlagerung der prototypischen Trisaccharide Lewis x und Blutgruppe H2 zu bestimmen. Die Struktursuche ergibt, dass die Fucose, die mit einer α (1→6)‐glykosidischen Bindung an die Galaktose gebunden ist, das wahrscheinlichste Produkt ist.
Publisher: Wiley
Date: 24-03-2022
Abstract: Im Laufe der COVID‐19 Pandemie haben mRNA‐basierte Impfstoffe an immenser Bedeutung gewonnen. Massenspektrometrie ist für die Entwicklung und Analyse von modifizierten RNA Molekülen unerlässlich, setzt jedoch ein grundlegendes Verständnis über Fragmentierungsprozesse voraus. Analog zu der Zersetzung von RNA in Lösung durch Autohydrolyse, kann die Spaltung des RNA Rückgrats ebenso in der Gasphase stattfinden. Bislang sind die Fragmentierungsmechanismen jedoch unzureichend untersucht. In dieser Arbeit wurden Intermediate aus isolierten RNA Dinukleotiden in der Gasphase generiert und mittels kryogener Infrarotspektroskopie in Helium‐Nanotröpfchen untersucht. Die experimentellen Daten, unterstützt durch Dichtefunktionaltheorie, liefern Hinweise dafür, dass die Bildung eines fünfgliedrigen zyklischen Phosphat‐Intermediats begünstigt ist, während lineare oder sechsgliedrige Strukturen ausgeschlossen werden können. Weiterhin zeigen die Experimente, dass eine zusätzliche, bekannte Reaktion von RNA Nukleotiden in Lösung auch in der Gasphase induziert werden kann: die Tautomerisierung von Cytosin. Die beiden beobachteten Reaktionen spiegeln daher universelle und intrinsische Eigenschaften der untersuchten Moleküle wider.
Publisher: American Chemical Society (ACS)
Date: 12-05-2021
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6CC01114D
Abstract: Differentiating the structure of isobaric glycopeptides represents a major challenge for mass spectrometry-based characterisation techniques.
Publisher: Wiley
Date: 02-03-2020
Publisher: Wiley
Date: 02-2019
DOI: 10.1002/MAS.21585
Publisher: American Chemical Society (ACS)
Date: 07-09-2021
Publisher: Wiley
Date: 22-06-2020
Publisher: Springer Science and Business Media LLC
Date: 06-05-2021
DOI: 10.1007/S00216-021-03334-3
Abstract: The position and configuration of carbon-carbon double bonds in unsaturated fatty acids is crucial for their biological functions and influences health and disease. However, double bond isomers are not routinely distinguished by classical mass spectrometry workflows. Instead, they require sophisticated analytical approaches usually based on chemical derivatization and/or instrument modification. In this work, a novel strategy to investigate fatty acid double bond isomers (18:1) without prior chemical treatment or modification of the ion source was implemented by non-covalent adduct formation in the gas phase. Fatty acid adducts with sodium, pyridinium, trimethylammonium, dimethylammonium, and ammonium cations were characterized by a combination of cryogenic gas-phase infrared spectroscopy, ion mobility-mass spectrometry, and computational modeling. The results reveal subtle differences between double bond isomers and confirm three-dimensional geometries constrained by non-covalent ion-molecule interactions. Overall, this study on fatty acid adducts in the gas phase explores new avenues for the distinction of lipid double bond isomers and paves the way for further investigations of coordinating cations to increase resolution. Graphical abstract
Publisher: Wiley
Date: 13-04-2022
Abstract: Fluorination is a potent method to modulate chemical properties of glycans. Here, we study how C3‐ and C6‐fluorination of glucosyl building blocks influence the structure of the intermediate of the glycosylation reaction, the glycosyl cation. Using a combination of gas‐phase infrared spectroscopy and first‐principles theory, glycosyl cations generated from fluorinated and non‐fluorinated monosaccharides are structurally characterized. The results indicate that neighboring group participation of the C2‐benzoyl protecting group is the dominant structural motif for all building blocks, correlating with the β‐selectivity observed in glycosylation reactions. The infrared signatures indicate that participation of the benzoyl group in enhanced by resonance effects. Participation of remote acyl groups such as Fmoc or benzyl on the other hand is unfavored. The introduction of the less bulky fluorine leads to a change in the conformation of the ring pucker, whereas the structure of the active dioxolenium site remains unchanged.
Publisher: Wiley
Date: 18-05-2020
Publisher: American Chemical Society (ACS)
Date: 24-04-2023
Publisher: Wiley
Date: 22-06-2020
Publisher: Wiley
Date: 24-04-2022
Publisher: Springer Science and Business Media LLC
Date: 20-03-2020
DOI: 10.1038/S41467-020-15284-Y
Abstract: Despite evident regulatory roles of heparan sulfate (HS) saccharides in numerous biological processes, definitive information on the bioactive sequences of these polymers is lacking, with only a handful of natural structures sequenced to date. Here, we develop a “ S hotgun” I on M obility M ass S pectrometry S equencing (SIMMS 2 ) method in which intact HS saccharides are dissociated in an ion mobility mass spectrometer and collision cross section values of fragments measured. Matching of data for intact and fragment ions against known values for 36 fully defined HS saccharide structures (from di- to decasaccharides) permits unambiguous sequence determination of validated standards and unknown natural saccharides, notably including variants with 3 O -sulfate groups. SIMMS 2 analysis of two fibroblast growth factor-inhibiting hexasaccharides identified from a HS oligosaccharide library screen demonstrates that the approach allows elucidation of structure-activity relationships. SIMMS 2 thus overcomes the bottleneck for decoding the informational content of functional HS motifs which is crucial for their future biomedical exploitation.
Publisher: Wiley
Date: 05-05-2023
Abstract: Fucose is a signaling carbohydrate that is attached at the end of glycan processing. It is involved in a range of processes, such as the selectin‐dependent leukocyte adhesion or pathogen‐receptor interactions. Mass‐spectrometric techniques, which are commonly used to determine the structure of glycans, frequently show fucose‐containing chimeric fragments that obfuscate the analysis. The rearrangement leading to these fragments—often referred to as fucose migration—has been known for more than 25 years, but the chemical identity of the rearrangement product remains unclear. In this work, we combine ion‐mobility spectrometry, radical‐directed dissociation mass spectrometry, cryogenic IR spectroscopy of ions, and density‐functional theory calculations to deduce the product of the rearrangement in the model trisaccharides Lewis x and blood group H2. The structural search yields the fucose moiety attached to the galactose with an α (1→6) glycosidic bond as the most likely product.
Publisher: American Chemical Society (ACS)
Date: 27-10-2022
DOI: 10.1021/JACS.2C05859
Publisher: American Chemical Society (ACS)
Date: 13-07-2020
DOI: 10.1021/ACS.ANALCHEM.0C02048
Abstract: Heparan sulfate and heparin are highly acidic polysaccharides with a linear sequence, consisting of alternating glucosamine and hexuronic acid building blocks. The identity of hexuronic acid units shows a variability along their sequence, as d-glucuronic acid and its
Publisher: Springer Science and Business Media LLC
Date: 28-01-2020
DOI: 10.1038/S41467-020-14424-8
Abstract: Detergents enable the purification of membrane proteins and are indispensable reagents in structural biology. Even though a large variety of detergents have been developed in the last century, the challenge remains to identify guidelines that allow fine-tuning of detergents for in idual applications in membrane protein research. Addressing this challenge, here we introduce the family of oligoglycerol detergents (OGDs). Native mass spectrometry (MS) reveals that the modular OGD architecture offers the ability to control protein purification and to preserve interactions with native membrane lipids during purification. In addition to a broad range of bacterial membrane proteins, OGDs also enable the purification and analysis of a functional G-protein coupled receptor (GPCR). Moreover, given the modular design of these detergents, we anticipate fine-tuning of their properties for specific applications in structural biology. Seen from a broader perspective, this represents a significant advance for the investigation of membrane proteins and their interactions with lipids.
Publisher: Wiley
Date: 03-06-2021
Abstract: In a previous work, we explored zone broadening and the achievable plate numbers in linear drift tube ion mobility‐mass spectrometry through developing a plate‐height model [1]. On the basis of these findings, the present theoretical study extends the model by exploring peak‐to‐peak resolution and peak capacity in ion mobility separations. The first part provides a critical overview of chromatography‐influenced resolution equations, including refinement of existing formulae. Furthermore, we present exact resolution equations for drift tube ion mobility spectrometry based on first principles. Upon implementing simple modifications, these exact formulae could be readily extended to traveling wave ion mobility separations and to cases when ion mobility spectrometry is coupled to mass spectrometry. The second part focuses on peak capacity. The well‐known assumptions of constant plate number and constant peak width form the basis of existing approximate solutions. To overcome their limitations, an exact peak capacity equation is derived for drift tube ion mobility spectrometry. This exact solution is rooted in a suitable physical model of peak broadening, accounting for the finite injection pulse and subsequent diffusional spreading. By borrowing concepts from the theoretical toolbox of chromatography, we believe that the present study will help in integrating ion mobility spectrometry into the unified language of separation science.
Publisher: American Chemical Society (ACS)
Date: 05-11-2020
Publisher: American Chemical Society (ACS)
Date: 02-09-2021
DOI: 10.1021/JACS.1C06944
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2SC06487A
Abstract: 3-Pyridylcarbinol ester derivatization introduces a universal probe for cryogenic gas-phase infrared spectroscopy of fatty acids that enables assignment of the position and configuration of carbon–carbon double bonds even in the presence of isomers.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Kevin Pagel.