Review
Biochemistry & Molecular Biology
Francisco Javier Canada, Angeles Canales, Pablo Valverde, Beatriz Fernandez de Toro, Monica Martinez-Orts, Paola Oquist Phillips, Amaia Pereda
Summary: Carbohydrates, either as free molecules or conjugated with other biomolecules, play important roles in various biological processes. Nuclear Magnetic Resonance spectroscopy (NMR) is a versatile tool for studying the structures and interactions of carbohydrates, providing information about their sequences, structures, and local geometries. Labeling carbohydrates with 13C enhances the resolution and detail of the analyzed structures. Moreover, combining NMR with molecular modeling and theoretical calculations offers insights into the conformational flexibility of carbohydrates. Additionally, the use of partially oriented media or paramagnetic perturbations allows for the study of longer and branched glycan chains. This review presents examples and an overview of recent and relevant NMR applications in the field of glycobiology.
CURRENT MEDICINAL CHEMISTRY
(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.
Review
Biochemistry & Molecular Biology
Javier Rojo, Pedro M. Nieto, Jose L. de Paz
Summary: Langerin is a C-type Lectin expressed on Langerhans cells that plays a crucial role in immune defense. It has the ability to recognize various carbohydrate ligands, including sulfated glycosaminoglycans (GAGs). Although there have been advancements in the synthesis of carbohydrate multivalent systems mimicking GAGs, there is limited research on their interaction with Langerin.
CURRENT MEDICINAL CHEMISTRY
(2022)
Review
Biophysics
Vanessa E. Abrantes-Coutinho, Andre O. Santos, Rafael B. Moura, Francisco N. Pereira-Junior, Lucia H. Mascaro, Simone Morais, Thiago M. B. F. Oliveira
Summary: Lectin-based biosensors have made significant progress in the field of electroanalysis, offering high sensitivity, specificity, precision, and stability for the detection of clinically relevant carbohydrates and glycoproteins. By combining different materials and functional groups, these sensors can further enhance detection performance and applicability.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2021)
Article
Biochemistry & Molecular Biology
Shivender Yadav, Kottari Naresh, Narayanaswamy Jayaraman
Summary: Glycovesicles are utilized as tools to study interactions at biological cell membranes, with ligand densities playing a key role in modulating these interactions. The study focused on mannose trisaccharide interacting with Con A and demonstrated different modes of interactions based on ligand density at the vesicle surface. Sub-nanomolar dissociation constants govern the intramolecular interaction within the vesicle plane, showing higher efficacy compared to aggregative intermolecular interactions.
Article
Chemistry, Multidisciplinary
Brian J. J. Timmer, Arjaan Kooijman, Xander Schaapkens, Tiddo J. Mooibroek
Summary: Galectins are a subclass of carbohydrate binding proteins that play a role in various biological processes. A synthetic galectin mimic with high selectivity for a specific galactoside has been designed and synthesized for the first time, showing a selectivity over 65-fold compared to a glucoside.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Uwe Osswald, Johannes Boneberg, Valentin Wittmann
Summary: Multivalent receptor-ligand binding is crucial in biological recognition processes. The incorporation of photoswitches into multivalent ligands enables the reversible change of spatial orientation, resulting in altered binding affinity and mode. This study presents a divalent ligand for wheat germ agglutinin (WGA) with an arylazopyrazole photoswitch, showing significant changes in lectin binding affinity and mode.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Oscar Francesconi, Francesco Milanesi, Cristina Nativi, Stefano Roelens
Summary: The study introduces a biomimetic receptor with unprecedented affinity for recognizing GlcNAc(2) in water, showing great selectivity among structurally related disaccharides and complete discrimination between mono- and disaccharides. Molecular modeling calculations supported by NOE data provided insights into the binding mode and origin of the affinities and selectivities exhibited by the receptor.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemical Research Methods
S. Chandra Shekar, Wancheng Zhao, Liyanage D. Fernando, Ivan Hung, Tuo Wang
Summary: The study presents a new method for analyzing the structure of carbohydrates using solid-state NMR. The method provides high resolution and allows for accurate resonance assignment of polysaccharides in plant and fungal cell walls using uniformly labeled cells. Long-range structural restraints can be obtained, which contributes to a better understanding of the spatial organization of plant cellulose microfibrils. The method has broad applications in the study of cellular carbohydrates and carbon-based biomaterials.
JOURNAL OF MAGNETIC RESONANCE
(2022)
Article
Chemistry, Multidisciplinary
Yuki Ohishi, Kentaro Masuda, Kazuki Kudo, Hajime Abe, Masahiko Inouye
Summary: Cage-shaped hosts and three-arm-shaped hosts exhibit strong binding to saccharides, with the latter being easier to prepare. Both types of hosts can form chiral complexes with high association constants and extract native monosaccharides into a lipophilic solvent.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Multidisciplinary Sciences
Shanshan Li, Kan-Yen Hsieh, Chiao- Kuo, Szu-Hui Lee, Grigore D. Pintilie, Kaiming Zhang, Chung- Chang
Summary: Lon is a evolutionarily conserved protease machine involved in degrading misfolded proteins and cellular substrates. Lon has a large N-terminal domain and forms a hexameric core of fused adenosine triphosphatase and protease domains. The structure of Lon engaging a substrate reveals a complex architecture with a unique tensegrity triangle and interlocked helices that act as a multipurpose platform for substrate access and unfolding.
Article
Chemistry, Multidisciplinary
Oscar Francesconi, Francesco Milanesi, Cristina Nativi, Stefano Roelens
Summary: In designing new biomimetic receptors for carbohydrates, shape-persistent macrocyclic structures are commonly chosen for effective recognition of neutral saccharides in water. However, this study found that acyclic receptors, while less explored, provide advantages in terms of selectivity for recognizing important 1,4-disaccharides in biological contexts. NMR spectroscopic data and molecular modeling calculations were used to analyze the differences in binding mode and shed light on the origin of recognition efficacy and selectivity.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Chemistry, Multidisciplinary
Masanori Nagao, Hikaru Matsumoto, Yoshiko Miura
Summary: Carbohydrates interact with corresponding lectins to participate in life activities. The binding between lectins and glycoconjugates on cell surfaces controls pathogen infection and cell activity regulation. Understanding the interactions of glycoconjugates has led to the development of therapeutic and preventive methods for infectious diseases. Glycopolymer, a class of materials containing multiple carbohydrates, allows for tuning of properties through molecular design. This review focuses on the design of glycopolymers over the past decade, aiming to develop inhibitors against pathogens and manipulators of cellular functions.
CHEMISTRY-AN ASIAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Irene Herrera-Gonzalez, Manuel Gonzalez-Cuesta, Michel Thepaut, Eugenie Laigre, David Goyard, Javier Rojo, Jose M. Garcia Fernandez, Franck Fieschi, Olivier Renaudet, Pedro M. Nieto, Carmen Ortiz Mellet
Summary: The carbohydrate chemical mimicry of sp2-iminosugars enables the synthesis of high-mannose-type oligosaccharide analogs whose solution and lectin bound conformations match those of the natural partners. The ability to finely modulate the binding affinity and selectivity towards specific lectins by incorporating the OMJ sp2-iminosugar caps offers potential applications in various fields.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Radoslav Z. Pavlovic, Remy F. Lalisse, Alexandar L. Hansen, Christopher A. Waudby, Zhiquan Lei, Murat Guney, Xiuze Wang, Christopher M. Hadad, Jovica D. Badjic
Summary: The molecular recognition processes of induced fit (IF) and conformational selection (CS) have been shown to play a central role in allosteric regulation in natural systems, where the substrate can either instruct the host to change its shape or the guest can select the optimal fit. A study demonstrated the potential interplay between the two mechanisms, providing insights for designing novel allosteric sequestering agents and chemosensors.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
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)
Review
Pharmacology & Pharmacy
Toni Todorovski, Daniela Kalafatovic, David Andreu
Summary: Infectious diseases caused by microbial pathogens are a major global health challenge, with viral infections being particularly notable due to the lack of effective drugs to combat their high mutation rate. The use of peptide-drug conjugates (PDCs) as targeted delivery systems has gained attention as a potential solution. This review discusses the current state of antiviral PDCs, focusing on the types of peptides and antiviral drugs used, as well as the challenges and future prospects of this class of therapeutics.
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
Entomology
Laura Regalado, Sara Sario, Rafael J. J. Mendes, Javier Valle, Peta J. J. Harvey, Catia Teixeira, Paula Gomes, David Andreu, Conceicao Santos
Summary: In this study, the biological activity of two underexplored spider venom peptides (J-atracotoxin-Hv1c and mu-theraphotoxin-Hhn2b) against adult D. suzukii flies was assessed, as well as the biological response of flies to these peptides through detoxification mechanisms. Results demonstrate that mu-theraphotoxin-Hhn2b enhanced fly longevity. Gene expression analysis suggests that detoxification and stress-related mechanisms are triggered in D. suzukii flies in response to treatment with these peptides. Our results highlight the potential of venom peptides to control D. suzukii and how to ultimately devise improved target-specific formulations.
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
Pharmacology & Pharmacy
Adam Carrera-Aubesart, Maria Gallo, Sira Defaus, Toni Todorovski, David Andreu
Summary: Bioactive peptides have gained recognition in biomedical areas due to their unique interactions with biological membranes. Topoisomeric peptides, made up of D-amino acids, provide a way to overcome protease degradation and mimic native peptide structures. This review focuses on recent advances in topoisomeric peptides with therapeutic applications, such as drug delivery and antimicrobial and anticancer activities, and discusses their interactions with membrane targets.
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
Biochemistry & Molecular Biology
Federica Nicolini, Toni Todorovski, Eduard Puig, Mireia Diaz-Lobo, Marta Vilaseca, Jesus Garcia, David Andreu, Ernest Giralt
Summary: Tumour suppressor p53 plays a crucial role in cancer development, but the tetramerisation mechanism of p53 is not fully understood. Mutations in p53, which occur in nearly 50% of cancers, can alter the oligomeric state of the protein and affect its biological function and cell fate decisions.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
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)
