Article
Polymer Science
Carlos Noble Jesus, Rhys Evans, Joe Forth, Carolina Estarellas, Francesco Luigi Gervasio, Giuseppe Battaglia
Summary: The study presents the design, simulation, synthesis, and reversible self-assembly of nanofibrils using polyhistidine-based oligopeptides. The inclusion of aromatic amino acids in the histidine block leads to the formation of amyloid-like fibrils with distinct antiparallel beta-strands. The structures undergo self-assembly in response to pH changes, offering potential for biotechnological and biomedical applications with pH-responsive fibrils in a physiologically relevant range.
Article
Multidisciplinary Sciences
Enrico Zurlo, Pravin Kumar, Georg Meisl, Alexander J. Dear, Dipro Mondal, Mireille M. A. E. Claessens, Tuomas P. J. Knowles, Martina Huber
Summary: Understanding the mechanism of amyloid protein assembly is crucial for studying neurodegenerative diseases. EPR method can directly measure the amount of intermediates during the aggregation process without the need for separation, providing insights into the kinetics of intermediate species formation and conversion. The study on alpha-synuclein aggregation using EPR revealed a large population of short-lived primary oligomers formed directly from monomeric species.
Article
Chemistry, Multidisciplinary
Eric H. L. Chen, Hsi-Wen Kao, Chih-Hsuan Lee, Jessica Y. C. Huang, Kuen Phon Wu, Rita P. Y. Chen
Summary: Fibrils of the hamster prion peptide have a unique structure with a water channel, and the three beta-strand segments are identified as the most amyloidogenic region that initiates fibrillization.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Jerome Gout, Floriane Meuris, Alain Desbois, Pierre Dorlet
Summary: In addition to copper and zinc, heme is believed to play a role in Alzheimer's disease. This study investigated the binding mode of heme to amyloid beta under different conditions, using isotopically labelled peptide and advanced spectroscopic methods. The results showed that the interaction between heme and amyloid beta leads to the formation of various species, suggesting that the binding site is not strong or highly specific.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Shean-Jaw Chiou, Huey-Jiun Ko, Chi-Ching Hwang, Yi-Ren Hong
Summary: Beta2-microglobulin (B2M) plays a crucial role in both immune response and antimicrobial activity, functioning primarily in innate defense. B2M acts as an antimicrobial peptide under acidic conditions, disrupting a wide range of microbes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Zhongju Ye, Zhao-Jun Yan, Chenhong Zhang, Jun-Li Hou, Shijing Yue, Lehui Xiao
Summary: Anti-A beta therapy has been the main focus in clinical trials for AD prevention and treatment. This study introduced a new strategy using a charged tubular supramolecule to suppress A beta fibrillation, showing efficient inhibition of A beta(40) fibrillation by CTS-A at a very low inhibitor:peptide molar ratio (1:10) and a reduced cytotoxic effect of A beta peptides post-inhibition or disaggregation. The organized supramolecular structure enhances amyloid fibrillar modulation, offering a new approach for AD treatment using supramolecules.
Article
Biochemistry & Molecular Biology
D. Santorelli, S. Rocchio, F. Fata, I Silvestri, F. Angelucci, F. Imperi, D. Marasco, C. Diaferia, L. Gigli, N. Demitri, L. Federici, A. Di Matteo, C. Travaglini-Allocatelli
Summary: The study found that ribosome-binding factor A folds via a 3-state mechanism in vitro and can form fibrils with a cross-beta structure. Additionally, the research suggests that the folding intermediate of PaRbfA may expose amyloidogenic regions, potentially acting as aggregation nuclei in fibril formation.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Multidisciplinary Sciences
Thinh D. N. Luong, Suhani Nagpal, Mourad Sadqi, Victor Munoz
Summary: This article introduces a method called "Molecular LEGO" that allows for the dissection of conformational landscapes of unbound intrinsically disordered proteins (IDPs) and provides insights into the functional mechanisms of these proteins. The method was applied to the protein NCBD and revealed specific energetic biases and conformational rheostatic behavior in NCBD's folding landscape, which are likely crucial for its function as a transcriptional coactivator.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Daniele Santorelli, Francesca Troilo, Francesca Fata, Francesco Angelucci, Nicola Demitri, Giorgio Giardina, Luca Federici, Flavia Catalano, Adele Di Matteo, Carlo Travaglini-Allocatelli
Summary: K-homology (KH) domains are structurally conserved domains found in proteins of different origins, which play important roles in various functions. Mutations in KH domains have been associated with multiple diseases, including fragile X syndrome. By characterizing the folding mechanism of a specific KH domain, it was found that transient intermediate accumulates and the domain has the propensity to form amyloid-like aggregates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Mikhail Matveyenka, Stanislav Rizevsky, Dmitry Kurouski
Summary: Lipid bilayers play a crucial role in the pathological assembly of amyloidogenic proteins and peptides, and unsaturated phospholipids catalyze the formation of more toxic amyloid aggregates.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Review
Chemistry, Physical
Nirbhik Acharya, Santosh Kumar Jha
Summary: The correct folding of proteins is crucial for their performance, and understanding the process of protein folding has been an important research topic for the past five decades. Wet molten globule (WMG) and dry molten globule (DMG) are two important intermediate states that play a key role in protein folding and unfolding reactions. While there is ample discussion about WMGs as a common unfolding intermediate, there is limited evidence for DMGs due to their near-native features and difficulty in studying them using global structural probes. This Review presents available literature and new evidence on DMGs to provide a broader perspective on their universality and discuss their significance in protein folding, function, and disease.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Review
Chemistry, Multidisciplinary
Yuxing Ma, Xiaofang Li, Ruoyang Zhao, Enqi Wu, Qiqige Du, Jun Guo, Liping Wang, Feng Zhang
Summary: DNA origami and protein origami can both create complex artificial nanostructures, but protein origami has an advantage in terms of versatility due to the limited number of nucleotides. Despite the similarities between peptides and DNA in structure and properties, using peptides instead of DNA to create complex bioactivities is still a challenge.
Article
Chemistry, Multidisciplinary
Gagandeep Singh, Manvir Kaur, Manpreet Singh, Harmandeep Kaur, Tejwant Singh Kang
Summary: This study reveals the role of time-dependent hydrolysis of [BF4](-) anion in ionic liquid [BF4] on inducing conformational changes in bovine serum albumin (BSA) and resulting in amyloid fiber formation. The addition of 10% IL in aqueous solution promotes the fibrillation of BSA most effectively among the investigated systems.
Review
Biochemistry & Molecular Biology
Parveen Salahuddin, Munazza Tamkeen Fatima, Vladimir N. Uversky, Rizwan Hasan Khan, Zeyaul Islam, Mohammad Furkan
Summary: Neurodegenerative diseases are characterized by the abnormal loss of neurons, with common pathogenic mechanisms involving misfolding and aggregation of proteins. Accumulating evidence suggests that amyloid oligomers, not fibrils, are the most toxic species causing AD and PD.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Chemistry, Physical
Monika Szefczyk, Natalia Szulc, Marlena Gasior-Glogowska, Dominika Bystranowska, Andrzej Zak, Andrzej Sikora, Oliwia Polanska, Andrzej Ozyhar, Lukasz Berlicki
Summary: In this paper, a hierarchical approach for constructing nanofibrils based on alpha,beta-peptide foldamers is proposed as a rational method for designing novel self-assembled nanomaterials. The incorporation of a specific amino acid residue resulted in the formation of helical foldamers, which was confirmed by spectroscopic techniques. The obtained alpha,beta-peptides showed a strong tendency to aggregate and form self-assembled nanostructures, as revealed by assays and microscopy. The location of the beta-amino acid in the coiled-coil structure affected the secondary structure and morphology of the self-assembled nanostructures.
Article
Chemistry, Analytical
Bianka Varnai, Marko Grabarics, Zoltan Szakacs, Kevin Pagel, Milo Malanga, Tamas Sohajda, Szabolcs Beni
Summary: The molecular-level interactions in the FDPX - NH2-β-CD systems were studied, revealing the formation of FDPX·NH2-β-CD complex at pD 7.4 and possibly multiple complexes at pD 2.0. Stability constants were determined by H-1 NMR titrations, showing a high-affinity system. Additionally, the acidic degradation of FDPX was investigated in detail for the first time.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Chemistry, Physical
Maike Lettow, Kim Greis, Marko Grabarics, Jan Horlebein, Rebecca L. Miller, Gerard Meijer, Gert von Helden, Kevin Pagel
Summary: Glycosaminoglycans (GAGs) play vital roles in biological processes and their characterization, particularly chondroitin and dermatan sulfate, poses challenges due to their varying sulfation patterns. Combining mass spectrometry and cryogenic infrared spectroscopy, researchers have identified that the degree and position of sulfate groups impact the conformational landscape in gas phase, providing insights for future sequencing approaches.
JOURNAL OF PHYSICAL CHEMISTRY A
(2021)
Article
Chemistry, Analytical
Marko Grabarics, Maike Lettow, Ansgar T. Kirk, Gert von Helden, Tim J. Causon, Kevin Pagel
Summary: This study extends the plate-height model to explore peak-to-peak resolution and peak capacity in ion mobility separations, providing exact resolution equations and a new peak capacity equation for drift tube ion mobility spectrometry. By refining existing formulas and overcoming limitations of constant assumptions, the study aims to integrate ion mobility spectrometry into the unified language of separation science through theoretical advancements borrowed from chromatography.
JOURNAL OF SEPARATION SCIENCE
(2021)
Review
Chemistry, Multidisciplinary
Marko Grabarics, Maike Lettow, Carla Kirschbaum, Kim Greis, Christian Manz, Kevin Pagel
Summary: Cells encode information in biopolymers, but little is known about the sugar code and biological roles of these molecules. The complexity of carbohydrate structures has made their analysis challenging, but recent advances in mass spectrometry have revolutionized glycan analysis.
Article
Biochemical Research Methods
Gergo Peter Szekeres, Kevin Pagel, Zsuzsanna Heiner
Summary: Analyzing the interactions between GAGs and cell membranes is challenging, but recent advancements in analytical methods and synthesis technology have made progress in this field. The development of laser technology, particularly nonlinear spectroscopic methods, such as vibrational sum-frequency generation spectroscopy, has the potential to unravel the complex structures of biological interfaces in real-time.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Carla Kirschbaum, Kim Greis, Sandy Gewinner, Wieland Schoellkopf, Gerard Meijer, Gert von Helden, Kevin Pagel
Summary: Tandem mass spectrometry plays a crucial role in elucidating lipid structures, with the coordination of silver ions enabling differentiation of glycerophospholipid isomers. Gas-phase infrared spectroscopy confirms the generation of dioxolane-type fragments from silver-adducted glycerophospholipids, providing qualitative explanations for the fragmentation behaviors of different isomers. This study demonstrates the significant contribution of gas-phase IR spectroscopy to understanding lipid dissociation mechanisms and the effects of coordinating cations.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Christian Manz, Michael Goetze, Clemens Frank, Andreas Zappe, Kevin Pagel
Summary: LC-MS is an important tool for the comprehensive characterization of N-glycans. However, the measurement times of HILIC chromatography remain a bottleneck in glycan analysis. This study demonstrates the use of an internal calibration strategy to speed up glycan analysis by reducing the number of utilized calibrant. The minimized calibrant shows accurate calibration and can be applied in HPLC runs without modification.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Kim Greis, Carla Kirschbaum, Martin I. Taccone, Michael Goetze, Sandy Gewinner, Wieland Schoellkopf, Gerard Meijer, Gert von Helden, Kevin Pagel
Summary: mRNA-based vaccines have become crucial during the COVID-19 pandemic. This study investigates the mechanism of backbone cleavage of RNA strands and the tautomerization of cytosine in the gas phase using experimental and theoretical approaches. The findings have important implications for the development and analysis of mRNA vaccines.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Kim Greis, Carla Kirschbaum, Giulio Fittolani, Eike Mucha, Rayoon Chang, Gert von Helden, Gerard Meijer, Martina Delbianco, Peter H. Seeberger, Kevin Pagel
Summary: This study investigates the influence of fluorination on the structure of the glycosyl cation, an intermediate in glycosylation reactions. The results reveal that C3 and C6 fluorination of glucosyl building blocks can alter the structure of the glycosyl cation, with neighboring group participation being the dominant motif.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Analytical
Christian Manz, Montserrat Mancera-Arteu, Andreas Zappe, Emeline Hanozin, Lukasz Polewski, Estela Gimenez, Victoria Sanz-Nebot, Kevin Pagel
Summary: Complex carbohydrates are common in nature and can have diverse structures, making their analysis challenging. Liquid chromatography combined with mass spectrometry is a common method for addressing this complexity, but ion mobility mass spectrometry has shown potential for distinguishing glycan isomers. Combining hydrophilic interaction liquid chromatography with IM-MS can be used to analyze glycan structures released from proteins, providing information on glycan composition and allowing for the distinction and quantification of glycan isomers with multiple sialic acids.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Kim Greis, Sabrina Leichnitz, Carla Kirschbaum, Chun-Wei Chang, Mei-Huei Lin, Gerard Meijer, Gert von Helden, Peter H. Seeberger, Kevin Pagel
Summary: The study investigates how the electron density in acyl protecting groups influences the stereoselectivity, revealing that electron-rich acylated galactose building blocks show higher alpha-selectivity, while counterparts with electron-withdrawing groups exhibit lower selectivity. Further research is needed to explore the mechanism behind this phenomenon.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Kim Greis, Caleb E. Griesbach, Carla Kirschbaum, Gerard Meijer, Gert von Helden, Kevin Pagel, Mark W. Peczuh
Summary: Ferrier reactions involve Lewis acid activation of a cyclic enol ether to generate a glycosyl Ferrier cation through the departure of an allylic leaving group. The resulting cation undergoes attack and transposition, forming a new acetal linkage. This study focuses on the septanosyl Ferrier cation derived from a seven-membered ring carbohydrate-based oxepine. Experimental characterization of the ion, including gas-phase cryogenic IR spectroscopy and solution-phase Ferrier reactions, reveals a preference for contraction to five-membered ring structures in the cation.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jerome Riedel, Gerard Meijer, Gert von Helden, Maike Lettow, Michael Gotze, Rebecca L. Miller, Geert-Jan Boons, Gergo Peter Szekeres, Kevin Pagel, Marko Grabarics
Summary: Glycosaminoglycans (GAGs), known for their diverse structures and importance in physiological processes, have gained attention in biochemical and biomedical research. Cryogenic gas-phase infrared (IR) spectroscopy has shown promise in identifying structural motifs of shorter GAG chains. This study used mass-selected heparan sulfate (HS) ions to extract characteristic vibrational features and employed random forest (RF) classifiers to discriminate between GAG classes and sulfate positions. The combination of gas-phase cryogenic IR ion spectroscopy and machine learning achieved high prediction accuracy for HS tetra- and hexasaccharides, demonstrating its importance in improving GAG sequencing and analysis of biomolecules.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemical Research Methods
Michael Goetze, Lukasz Polewski, Leila Bechtella, Kevin Pagel
Summary: This article introduces a 3D-printable nano-electrospray ionization (nano-ESI) source for Bruker instruments, which can be assembled by anyone with access to a 3D printer. The source can be fitted to any Bruker mass spectrometer with an ionBooster ESI source and only requires minor, reversible changes to the original Bruker hardware. The general utility of the source was demonstrated by recording high-resolution MS spectra of small molecules, intact proteins, as well as complex biological samples in negative and positive ion mode on two different Bruker instruments.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Biochemistry & Molecular Biology
Ahed Almalla, Laura Elomaa, Lei''la Bechtella, Assal Daneshgar, Prabhu Yavvari, Zeinab Mahfouz, Peter Tang, Beate Koksch, Igor Sauer, Kevin Pagel, Karl Herbert Hillebrandt, Marie Weinhart
Summary: In this study, the potential of proteolytic enzymes including pepsin, papain, alpha-amylase, and collagenase to solubilize porcine liver dECM was compared. Papain, a plant-derived enzyme, was found to be a cost-effective alternative to animal-derived pepsin for dECM solubilization. Papain-digested dECM preserved its thermally triggered gelation properties similar to pepsin-digested dECM, and the resulting hydrogels demonstrated enhanced bioadhesiveness.