Article
Chemistry, Multidisciplinary
Sinead McCann, William E. Roe, Hannah E. Agnew, Peter C. Knipe
Summary: To imitate the dynamic molecules in biological systems, foldamers need to possess stimulus-responsive behavior. In this study, we present a foldamer architecture based on alternating pyridine-diketopiperazine linkers. Epimerization is prevented via a copper-catalyzed coupling protocol. The native conformation of the compounds is initially investigated in both solid and solution states. The foldamers can be solubilized in DMSO and pH 9.5 buffer while retaining conformational control. Furthermore, dynamic switching is demonstrated through acid treatment, resulting in stimulus-responsive sidechain reconfiguration.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
P. P. Kobchikova, S. Efimov, I. A. Khodov, V. V. Klochkov
Summary: In this study, cyclosporins D, E, and G were characterized by NMR spectroscopy and molecular dynamics simulation to investigate their structure features and backbone flexibility. It was found that these peptides share common characteristics, with the exception of CsE, which lacks backbone dynamics at the nanosecond timescale, raising questions about its biological activity.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Chemistry, Multidisciplinary
Albert A. Smith, Emelyne M. Pacull, Sabrina Stecher, Peter W. Hildebrand, Alexander Vogel, Daniel Huster
Summary: G protein-coupled receptors initiate signal transduction by binding with ligands. In this study, we focus on the growth hormone secretagogue receptor (GHSR), which binds with the 28 residue peptide ghrelin. We compared the dynamics of apo and ghrelin-bound GHSR using long molecular dynamics simulation trajectories and identified differences in dynamics in specific regions. We also investigated the traversal of GHSR over a rugged energy landscape via principal component analysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Kris Strunge, Tucker Burgin, Thaddeus W. Golbek, Steven J. Roeters, Jim Pfaendtner, Tobias Weidner
Summary: α-synuclein folds into a defined secondary structure at the air-water interface, promoting its aggregation and fibrillation. Understanding the role of hydrophobic surfaces in this process is important for studying severe brain disorders such as Parkinson's disease.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Alida Besch, William M. Marsiglia, Moosa Mohammadi, Yingkai Zhang, Nathaniel J. Traaseth
Summary: Many human cancers are treated with small molecule inhibitors that target the kinase domain of receptor tyrosine kinases. Long-term treatment often leads to drug resistance mutations at the gatekeeper residue, increasing the aggressiveness of the cancer. However, the mechanism of gain-of-function by gatekeeper mutations is poorly understood.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Applied
Adele Vanacore, Maria Concetta Forgione, Domenico Cavasso, Ha Ngoc Anh Nguyen, Antonio Molinaro, James P. Saenz, Gerardino D'Errico, Luigi Paduano, Roberta Marchetti, Alba Silipo
Summary: Methylobacterium extorquens strain PA1 secretes a diverse mixture of exopolysaccharides (EPSs), which may contribute to increased methanol tolerance and cell stability.
CARBOHYDRATE POLYMERS
(2022)
Article
Chemistry, Applied
O. N. Makshakova, E. R. Safarova, Y. F. Zuev
Summary: This study investigated the molecular interactions between RNase and polysaccharides, revealing the impact of polysaccharide side chains on protein structure in complexes. Computational simulations and spectroscopic analyses confirmed stable interactions, with potential implications for using rhamnogalacturonan I as a matrix material for protein delivery systems.
CARBOHYDRATE POLYMERS
(2021)
Article
Biochemistry & Molecular Biology
Carlos A. Elena-Real, Annika Urbanek, Lionel Imbert, Anna Morato, Aurelie Fournet, Frederic Allemand, Nathalie Sibille, Jerome Boisbouvier, Pau Bernado
Summary: A strategy for efficiently assigning frequencies to individual nuclei in large biomolecular machines and repetitive proteins using in vitro protein expression is presented. The approach was demonstrated to be applicable for NMR assignment in four proteins by introducing isotopically labeled alanines. The labeling method enabled unambiguous assignments in large protein assemblies and revealed the correlation between helical stability and homorepeat length in Phox2B. Selectively introducing alanines with distinct labeling patterns proves to be a powerful tool for studying challenging biomolecular systems.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Federica Maschietto, Erik Zavala, Brandon Allen, J. Patrick Loria, Victor Batista
Summary: In this study, computational modeling and solution NMR spectroscopy were combined to identify an allosteric site in MptpA. The findings suggest that this site plays a crucial role in substrate binding and reaction kinetics.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Physical
Yi Ji, Zhengmao Liu, Zhenchao Zhao, Pan Gao, Xinhe Bao, Kuizhi Chen, Guangjin Hou
Summary: The study investigates the molecular dynamics of molecules in MFI zeolites and finds that the structural differences have a significant impact on shape selectivity. In the absence of acid sites, molecules can only diffuse along straight channels and tend to occupy channel intersections. Different types of pore confinements result in different dynamic motions of the molecules. With the presence of acid sites, molecules are strongly adsorbed and their motions are further impeded.
Article
Chemistry, Medicinal
Yoseph Atilaw, Vasanthanathan Poongavanam, Caroline Svensson Nilsson, Duy Nguyen, Anja Giese, Daniel Meibom, Mate Erdelyi, Jan Kihlberg
Summary: PROTACs induce intracellular degradation of target proteins through a bifunctional structure. Structural insights into a VHL-based PROTAC revealed elongated and polar conformations in solutions, suggesting the importance of molecular chameleonicity for cell permeability.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Bruno Linclau, Zhong Wang, Benjamin Jeffries, Jerome Graton, Rodrigo J. Carbajo, Davy Sinnaeve, Jean-Yves Le Questel, James S. Scott, Elisabetta Chiarparin
Summary: Efficient drug discovery relies on optimizing bioactivity and compound properties such as lipophilicity, guided by efficiency metrics; the use of conformer-specific lipophilicities is a less explored strategy; optimizing lipophilicity values for different conformers can create a novel avenue in drug discovery.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Polymer Science
Yiqing Wang, Xiao Tan, Adil Usman, Yuhao Zhang, Michal Sawczyk, Petr Kral, Cheng Zhang, Andrew K. Whittaker
Summary: A major challenge in the preparation of polymeric F-19 MRI contrast agents is signal attenuation caused by reduced segmental mobility of partly fluorinated polymers. This study focuses on the role of hydrophilic segments in imaging performance and explores the effect of different hydrophilic segments on F-19 imaging. The results highlight the importance of maintaining high fluorine visibility and long T-2 relaxation time for effective CAs.
Article
Chemistry, Multidisciplinary
Shun Dekura, Motohiro Mizuno, Hatsumi Mori
Summary: A salt with a three-dimensional hydrogen-bonded phosphate network and imidazolium cations was found to exhibit isotropic anhydrous superprotonic conductivity exceeding 10(-3) S cm(-1), which is achieved through the accelerated molecular motion along the proton conduction pathway.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Mayra Queme-Pena, Tunde Juhasz, Gergely Kohut, Maria Ricci, Priyanka Singh, Imola Cs Szigyarto, Zita Papp, Livia Fulop, Tamas Beke-Somfai
Summary: Anticancer peptides have advantages targeting cell membranes, with three distinct binding modes identified: surface helical structure, partially helical structure with disordered regions, and non-inserted helical monomeric form.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Reyes Nunez-Franco, Gonzalo Jimenez-Oses, Jesus Jimenez-Barbero, Francisca Cabrera-Escribano, Antonio Franconetti
Summary: A multidisciplinary study is conducted to investigate the pi-pi interactions established by pyrylium frameworks as pi-hole donors. The combination of CSD analysis, computational modelling, and experimental NMR spectroscopy data provides essential information on the key parameters characterizing these interactions, paving the way for further applications of this versatile heterocycle.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Medicinal
Marta G. Lete, Antonio Franconetti, Sandra Delgado, Jesus Jimenez-Barbero, Ana Arda
Summary: This study investigated the interaction between glycosphingolipids (GSLs) and galectins using liposomes as membrane mimicking scaffolds. The results showed different binding capacities of galectins towards glycans depending on whether they were free oligosaccharides or part of GSL inserted into a lipid bilayer.
Article
Chemistry, Multidisciplinary
Francesco Milanesi, Luca Unione, Ana Arda, Cristina Nativi, Jesus Jimenez-Barbero, Stefano Roelens, Oscar Francesconi
Summary: Glycomics research has revealed the essential role of carbohydrates in biological systems and the importance of chemical tools in studying glycan function. While biomimetic receptors can selectively bind to simple saccharides, this study demonstrates the unprecedented recognition of a complex glycopeptide by a biomimetic receptor. The receptor shows high affinity for the core disaccharide of the N-glycan and has the potential for versatile applications in glycoscience.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Marta G. Lete, Antonio Franconetti, Sara Bertuzzi, Sandra Delgado, Mikel Azkargorta, Felix Elortza, Oscar Millet, Gonzalo Jimenez-Oses, Ana Arda, Jesus Jimenez-Barbero
Summary: Fluorine (F-19) incorporation into lectins has allowed monitoring of carbohydrate binding through NMR spectroscopy. Galectin-3 (Gal3) and Galectin-8 (Gal8) with one and two carbohydrate recognition domains (CRDs), respectively, were chosen. The presence of fluorine did not significantly affect glycan binding affinity, and allowed differentiation of binding events at different sites within the same lectin.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Fanji Kong, Pablo Rios, Conner Hauck, Francisco Jose Fernandez-de-Cordova, Diane A. Dickie, Laurel G. Habgood, Amor Rodriguez, T. Brent Gunnoe
Summary: We have demonstrated the dimerization and oligomerization reactions of ethylene using bis(phosphino)boryl supported Ni(II) complexes as catalyst precursors. The addition of alkylaluminum(III) compounds or other Lewis acid additives enhances the activity and selectivity of these Ni(II) complexes, leading to the production of butenes and higher olefins. Our studies suggest that this catalysis involves a cooperative activation of ethylene by the Ni-B unit, resulting in the formation of a key borametallacycle intermediate.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Ana Pozo-Rodriguez, Juan A. A. Mendez-Liter, Rocio Garcia-Villalba, David Beltran, Eva Calvino, Andres G. Santana, Laura I. I. De Eugenio, Francisco Javier Canada, Alicia Prieto, Jorge Barriuso, Francisco A. A. Tomas-Barberan, Maria Jesus Martinez
Summary: Resveratrol was glycosylated by using rXynSOS-E236G glycosynthase, resulting in the production of 3-O-beta-D-xylobiosyl resveratrol as the major product. Response surface methodology was used to optimize the reaction, yielding 35% of 3-O-beta-D-xylobiosyl resveratrol. Xylobiosylation decreased the antioxidant capacity of resveratrol, but significantly improved its solubility for improved delivery and transit to the colon.
Article
Nanoscience & Nanotechnology
Anna Blasi-Romero, Molly Angstrom, Antonio Franconetti, Taj Muhammad, Jesus Jimenez-Barbero, Ulf Goransson, Carlos Palo-Nieto, Natalia Ferraz
Summary: This study combines the wound-healing properties of KR-12 peptide with wood-derived cellulose nanofibrils (CNFs) to create bioactive materials for treating chronic wounds. Different coupling chemistries were used to covalently attach KR-12 derivatives onto CNFs, and the bioactivity of KR12-CNF conjugates was evaluated in terms of antibacterial activities and anti-inflammatory effects. The results showed that thiol-ene chemistry produced the most bioactive conjugates, attributed to favorable peptide conformation and accessibility. This study advances the development of CNF-based materials for chronic wound care and provides insights into the effect of conjugation chemistry on the bioactivity of host defense peptides.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Zhen Wang, Ana Poveda, Qingju Zhang, Luca Unione, Herman S. Overkleeft, Gijsbert A. van der Marel, Jimenez-Barbero Jesus, Jeroen D. C. Codee
Summary: Researchers have successfully synthesized a series of polysaccharide fragments with a unique structure that can activate T cells and bind to specific receptors. Detailed structural studies have revealed the secondary structure of these fragments, providing a basis for further understanding their mode of action.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Matteo A. . Tallarida, Fabrizio Olivito, Claudio D. Navo, Vincenzo Algieri, Antonio Jiritano, Paola Costanzo, Ana Poveda, Maria J. Moure, Jesus Jimenez-Barbero, Loredana Maiuolo, Gonzalo Jimenez-Oses, Antonio De Nino
Summary: The synthesis of polysubstituted spirocyclopropyl oxindoles using rare-earth metal (REM) salts, particularly Sc(OTf)3, was achieved with high diastereoselectivity (<= 94:6:0:0) in a multicomponent reaction. Density functional theory calculations on the model reaction confirmed the observed selectivity and demonstrated that the coordinating capabilities and oxophilicity of the metal played a crucial role in inducing the formation of one main diastereoisomer.
Article
Biochemistry & Molecular Biology
Hans-Christian Siebert, Thomas Eckert, Anirban Bhunia, Nele Klatte, Marzieh Mohri, Simone Siebert, Anna Kozarova, John W. Hudson, Ruiyan Zhang, Ning Zhang, Lan Li, Konstantinos Gousias, Dimitrios Kanakis, Mingdi Yan, Jesus Jimenez-Barbero, Tibor Kozar, Nikolay E. Nifantiev, Christian Vollmer, Timo Brandenburger, Detlef Kindgen-Milles, Thomas Haak, Athanasios K. Petridis
Summary: The global outbreak of SARS-CoV-2/COVID-19 has provided an opportunity and challenge to accumulate a large amount of biomedical data and test new concepts and strategies to combat the pandemic. This study correlated clinical biomedical data with structural biology and biophysical data to evaluate new diagnostic and therapeutic approaches against SARS-CoV-2. The methods used were effective in identifying potential peptide sequences and carbohydrate moieties to protect the blood-brain barrier and develop new therapeutic approaches against long-COVID symptoms.
Article
Chemistry, Multidisciplinary
Angeles Canales, Javier Sastre, Jose M. Orduna, Cindy M. Spruit, Javier Perez-Castells, Gema Dominguez, Kim M. Bouwman, Roosmarijn van der Woude, Francisco Javier Canada, Corwin M. Nycholat, James C. Paulson, Geert-Jan Boons, Jesus Jimenez-Barbero, Robert P. de Vries
Summary: Influenza virus infection remains a threat to human health due to the drifting of viral hemagglutinins, which evade infection and vaccine-induced antibody responses. Recent H3N2 and pandemic H1 viruses specifically recognize glycan structures containing at least three N-acetyllactosamine units. This study characterizes the glycan specificity of H1 variants, including the one responsible for the 2009 pandemic outbreak, and investigates the preference for tri-LacNAc motifs in human-type receptor-adapted viruses using glycan arrays, tissue binding analyses, and nuclear magnetic resonance experiments.
Article
Chemistry, Multidisciplinary
Giulio Fittolani, Theodore Tyrikos-Ergas, Ana Poveda, Yang Yu, Nishu Yadav, Peter H. Seeberger, Jesus Jimenez-Barbero, Martina Delbianco
Summary: This article introduces a synthetic glycan molecule that adopts a stable secondary structure not found in nature, called a glycan hairpin. The synthetic glycan is created by combining natural glycan motifs and utilizing unconventional hydrogen bonds and hydrophobic interactions. Nuclear magnetic resonance conformational analysis and long-range inter-residue nuclear Overhauser effects confirm the folded conformation of the synthetic glycan hairpin. The ability to control the 3D shape of glycans has the potential to provide more foldamer scaffolds with programmable properties and functions.
Review
Chemistry, Multidisciplinary
Jon I. Quintana, Unai Atxabal, Luca Unione, Ana Arda, Jesus Jimenez-Barbero
Summary: Nuclear Magnetic Resonance (NMR) is widely used to study glycan-protein molecular recognition events, providing qualitative and quantitative information at different levels of resolution and complexity. However, the weak affinity of lectin-sugar interactions is overcome by multivalency in biological processes. The application of NMR methods to monitor multivalent lectin-glycan interactions is challenging due to the disappearance of NMR signals when large macromolecular complexes are formed.
CHEMICAL SOCIETY REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
Carlo Pifferi, Leire Aguinagalde, Ane Ruiz-de-Angulo, Nagore Sacristan, Priscila Tonon Baschirotto, Ana Poveda, Jesus Jimenez-Barbero, Juan Anguita, Alberto Fernandez-Tejada
Summary: The overexpression of aberrantly glycosylated tumor-associated mucin-1 (TA-MUC1) in human cancers makes it a major target for the development of anticancer vaccines derived from synthetic MUC1-(glyco)peptide antigens. However, glycopeptide-based subunit vaccines are weakly immunogenic, requiring adjuvants and/or additional immunopotentiating approaches to generate optimal immune responses.
Article
Immunology
Leticia Martin-Cruz, Marcos Vinuela, Ioanna Kalograiaki, Alba Angelina, Paola Oquist-Phillips, Irene Real-Arevalo, Francisco Javier Canada, Jose Ignacio Tudela, Luis Molto, Jesus Moreno-Sierra, Jose Luis Subiza, Oscar Palomares
Summary: This study reveals novel molecular mechanisms by which heparan sulfate-related structures associated with tumor cells promote the generation of functional Tregs in cancer. Furthermore, the presence of a circulating human Ca10 counterpart (Ca10H) in cancer patients and its correlation with tumor size and metastasis suggests important clinical implications in cancer treatment.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)