Article
Chemistry, Multidisciplinary
Prashant Jain, Chethan D. Shanthamurthy, Shani Leviatan Ben-Arye, Robert J. Woods, Raghavendra Kikkeri, Vered Padler-Karavani
Summary: Selective inhibition of chemokines using structurally defined heparan sulfate oligosaccharides can provide insights into cancer cell migration and metastasis. Rational design and synthesis of N-unsubstituted and N-acetylated heparan sulfate tetrasaccharides have shown selective inhibition of structurally homologous chemokines.
Article
Chemistry, Multidisciplinary
Mohit Chhabra, Gareth G. Doherty, Nicholas W. See, Neha S. Gandhi, Vito Ferro
Summary: Heparan sulfate is a complex polysaccharide widely expressed on cell surfaces and in the extracellular matrix, interacting with numerous proteins to mediate various biological and pathological processes. Developing synthetically tractable HS mimetics with fewer side effects has become an attractive approach for treating cancer and infectious diseases.
Article
Chemistry, Organic
Wei Liu, Zhifei Hu, Peng Xu, Biao Yu
Summary: Here, we presented a convenient procedure to prepare EPP glycosides and their application in the synthesis of the clinically approved anticoagulant fondaparinux. Additionally, we successfully achieved the synthesis of heparin-like tetrasaccharides using EPP glycosides in a one-pot orthogonal glycosylation reaction.
Review
Neurosciences
Jacob Alexander, Gizem Keles, Jessica Killingsworth, Ronald Bronson, Christine Perez, Darrell Sawmiller, R. Douglas Shytle
Summary: Developmental disabilities are disorders that limit function due to impaired nervous system development, including learning, language, behavior, or physical abilities. The prevalence of autism spectrum disorder (ASD) is high, and it may be related to deficient levels of heparan sulfate (HS).
EXPERIMENTAL NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Maria De Risi, Michele Tufano, Filomena Grazia Alvino, Maria Grazia Ferraro, Giulia Torromino, Ylenia Gigante, Jlenia Monfregola, Elena Marrocco, Salvatore Pulcrano, Lea Tunisi, Claudia Lubrano, Dulce Papy-Garcia, Yaakov Tuchman, Alberto Salleo, Francesca Santoro, Gian Carlo Bellenchi, Luigia Cristino, Andrea Ballabio, Alessandro Fraldi, Elvira De Leonibus
Summary: Lysosomal storage disorders, characterized by altered metabolism of heparan sulfate, cause autistic symptoms followed by dementia in children. The study found that embryonic dopaminergic neurodevelopmental defects due to altered function of heparan sulfate lead to autistic behaviors in mice.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Tanja Gerlza, Christina Trojacher, Nikola Kitic, Tiziana Adage, Andreas J. Kungl
Summary: Heparan sulfate proteoglycans (HSPGs) are widely distributed in human tissues, playing important roles in cell-cell communication. They are of therapeutic interest in cancer, inflammation, and infectious diseases. Current medical approaches aim to antagonize HSPG function in pathology.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2021)
Review
Biochemistry & Molecular Biology
Anthony J. J. Hayes, James Melrose
Summary: Heparan sulfate is a complex glycosaminoglycan that plays important roles in various biological processes through interactions with extracellular ligands and cellular receptors. Its chain lengths and sequences can vary, providing structural diversity. Heparan sulfate has regulatory properties in tissue development, wound healing, immune regulation, inflammation, and tumor development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Catarina Marques, Celso A. Reis, Romain R. Vives, Ana Magalhaes
Summary: Heparan Sulfate Proteoglycans (HSPGs) play important roles in orchestrating cellular events in physiology and pathology by modulating cell signaling networks and cell interactions. The structural features of HS chains are crucial for the functions of HSPGs, influencing protein interactions and signaling. The tightly controlled biosynthetic pathway of HS leads to structural diversity, which is differently regulated in various tissues, developmental stages, and pathologies such as cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Casper de Boer, Zachary Armstrong, Vincent A. J. Lit, Uri Barash, Gijs Ruijgrok, Ilanit Boyango, Merle M. Weitzenberg, Sybrin P. Schroder, Alexi J. C. Sarris, Nico J. Meeuwenoord, Pedro Bule, Yasmine Kayal, Neta Ilan, Jeroen D. C. Codee, Israel Vlodavsky, Herman S. Overkleeft, Gideon J. Davies, Liang Wu
Summary: Research has shown that by developing effective HPSE inhibitors, extracellular HPSE activity can be reduced, thereby reducing the aggressiveness of cancer and potentially controlling pathological HPSE-driven malignancies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Lakshmi N. R. Thota, Joaquin E. Lopez Rosales, Ivan Placencia, Evgeny A. Zemskov, Paola Tonino, Ashley N. Michael, Stephen M. Black, Andreia Z. Chignalia
Summary: The endothelial glycocalyx is an important signaling layer involved in cellular homeostasis. Its diverse composition and relative contributions of its constituents to overall function are still not well understood. The deletion of glypican 1, a glycocalyx component, results in a modified glycocalyx without affecting baseline lung endothelial function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rupert Derler, Nikola Kitic, Tanja Gerlza, Andreas J. Kungl
Summary: This study isolated and characterized heparan sulfate from human lung tissues, identifying syndecans as the predominant proteoglycan class in human lungs. The disaccharide composition was found to vary among individuals according to sex, age, and health stage. Differences in the composition affected the binding affinities of chemokines, suggesting selective immune cell responses depending on the relative chemokine-glycan affinities. This provides important new insights for potentially developing individualized therapies for lung immunological disorders targeting HS.
Article
Neurosciences
Susan L. Lindsay, George A. McCanney, Jiangshan Zhan, Miriam Scheld, Rebecca Sherrard Smith, Carl S. Goodyear, Edwin A. Yates, Markus Kipp, Jeremy E. Turnbull, Susan C. Barnett
Summary: There is an urgent need for therapies that target the multicellular pathology of central nervous system (CNS) disease. Modified, nonanticoagulant heparins mimic the heparan sulfate glycan family and are known regulators of multiple cellular processes. In vitro studies demonstrate the potential of low sulfated modified heparin mimetics (LS-mHeps) for repairing CNS demyelination. LS-mHep7, an in vitro lead compound, shows promising results in experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination by promoting faster recovery, reducing inflammation, and restoring animal weight. The potential mechanism of action involves sequestering inflammatory cytokines, such as CCL5, which are elevated during immune-mediated inflammatory attacks.
Article
Medicine, Research & Experimental
Stefan Lennard Krautschneider, Fabian M. Troschel, Eduardo Vadillo, Hans Theodor Eich, Martin Goette, Nancy Adriana Espinoza-Sanchez, Burkhard Greve
Summary: This study aimed to investigate the interplay between heparan sulfate (HS) degradation and radiation response in triple-negative breast cancer (TNBC) cells. The results showed significantly increased radioresistance and cell migration after HS degradation. Furthermore, the expression and activation of certain signaling pathway molecules were altered after HS degradation, impacting the radiation resistance of TNBC cells.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ruben Casatejada-Anchel, Jesus Munoz-Bertomeu, Sara Rosa-Tellez, Armand D. Anoman, Sergio G. Nebauer, Alejandro Torres-Moncho, Alisdair R. Fernie, Roc Ros
Summary: The Phosphorylated Pathway of Serine Biosynthesis (PPSB) plays a crucial role in plant growth and metabolism, with PGDH2 and PGDH3 impacting plant development. PGDH2 has a stronger effect on plant growth compared to PGDH3, while the latter may have additional functions in photosynthetic cells.
Article
Chemistry, Multidisciplinary
Anil K. Gorle, Thomas Haselhorst, Samantha J. Katner, Arun Everest-Dass, James D. Hampton, Erica J. Peterson, Jennifer E. Koblinski, Eriko Katsuta, Kazuaki Takabe, Mark von Itzstein, Susan J. Berners-Price, Nicholas P. Farrell
Summary: The 1:1 adduct of the pentasaccharide Fondaparinux and the substitution-inert polynuclear platinum complex TriplatinNC was found to modulate the geometry around glycosidic linkages, potentially inhibiting heparan sulfate cleavage in breast cancer cells and metastasis in an animal model. This study provides insights into a novel approach for designing platinum drugs with intrinsic anti-metastatic potential.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Thomas Senage, Anu Paul, Thierry Le Tourneau, Imen Fellah-Hebia, Marta Vadori, Salam Bashir, Manuel Galinanes, Tomaso Bottio, Gino Gerosa, Arturo Evangelista, Luigi P. Badano, Alberto Nassi, Cristina Costa, Galli Cesare, Rizwan A. Manji, Caroline Cueff de Monchy, Nicolas Piriou, Romain Capoulade, Jean-Michel Serfaty, Guillaume Guimbretiere, Etienne Dantan, Alejandro Ruiz-Majoral, Guenola Coste du Fou, Shani Leviatan Ben-Arye, Liana Govani, Sharon Yehuda, Shirley Bachar Abramovitch, Ron Amon, Eliran Moshe Reuven, Yafit Atiya-Nasagi, Hai Yu, Laura Iop, Kelly Casos, Sebastian G. Kuguel, Arnau Blasco-Lucas, Eduard Permanyer, Fabrizio Sbraga, Roger Llatjos, Gabriel Moreno-Gonzalez, Melchor Sanchez-Martinez, Michael E. Breimer, Jan Holgersson, Susann Teneberg, Marta Pascual-Gilabert, Alfons Nonell-Canals, Yasuhiro Takeuchi, Xi Chen, Rafael Manez, Jean-Christian Roussel, Jean-Paul Soulillou, Emanuele Cozzi, Vered Padler-Karavani
Summary: In a large cohort of patients who underwent aortic valve replacement, antibody responses to glycans present in bioprosthetic heart valves, notably galactose-alpha 1,3-galactose and N-glycolylneuraminic acid, were implicated in valve calcification and deterioration. It was found that antibodies against xenoantigens galactose-alpha 1,3-galactose and N-glycolylneuraminic acid could mediate the deterioration of bioprosthetic heart valves through calcification. Results suggest that BHVs manufactured using donor tissues deficient in these antigens may have improved durability.
Article
Biochemistry & Molecular Biology
Suraj Toraskar, Preeti Madhukar Chaudhary, Raghavendra Kikkeri
Summary: This study investigated the impact of the size and shape of gold nanoparticles on carbohydrate antigen processing and immune response, revealing that spherical and star-shaped gold nanoparticles displayed superior immune response-inducing properties compared to rod-shaped nanoparticles.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Steven J. Berardinelli, Alexander Eletsky, Jessika Valero-Gonzalez, Atsuko Ito, Rajashri Manjunath, Ramon Hurtado-Guerrero, James H. Prestegard, Robert J. Woods, Robert S. Haltiwanger
Summary: This article investigates the mechanism of O-fucosylation modification of thrombospondin type-1 repeats (TSRs) in the endoplasmic reticulum (ER) quality control. Molecular dynamics simulations, crystallography, and NMR experiments provide evidence that the Glucose-Fucose disaccharide interacts with specific amino acids in the TSR3 domain, protecting a nearby disulfide bond. These findings reveal the importance of O-fucosylation modification in maintaining TSR stability.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Ariel Shitrit, Sandhya Mardhekar, Israel Alshanski, Prashant Jain, Rakesh Raigawali, Chethan D. Shanthamurthy, Raghavendra Kikkeri, Shlomo Yitzchaik, Mattan Hurevich
Summary: This study investigated the relationship between Heparan sulfate glycosaminoglycans and the binding of heavy metal ions using electrochemical and surface characterization techniques. It was found that the uronic acid type and sulfation pattern play a crucial role in the binding of Hg(II), Cd(II), and Pb(II).
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Sandhya Mardhekar, Balamurugan Subramani, Prasanna Samudra, Priyadharshini Srikanth, Virendrasinh Mahida, Preeti Ravindra Bhoge, Suraj Toraskar, Nixon M. Abraham, Raghavendra Kikkeri
Summary: The sulfation patterns on HS and CS regulate receptor-mediated homing of nanoprobes in primary and secondary cells. Aggressive cancer cells displayed a strong uptake of GAG-nanoprobes, while other cells showed selective or preferential uptake of CS-E-coated nanoprobes.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Multidisciplinary Sciences
Xiaocong Wang, Melinda S. Hanes, Richard D. Cummings, Robert J. Woods
Summary: Sulfated glycans have significant potential in molecular pathology as biomarkers for various diseases. However, there is a lack of sulfate-recognizing lectins. In this study, a mutated form of E-selectin was engineered using computational approaches, which showed highly specific recognition of 6'-sulfo-sLex. The mutations in the recombinant lectin eliminated repulsions with the sulfate moiety and abolished interactions with the endogenous ligand.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Ankita Chandra, Preeti Ravindra Bhoge, K. R. Chethan, Chethan D. D. Shanthamurthy, Raghavendra Kikkeri
Summary: In this study, highly fluorescent gold nanoclusters were engineered with sulfated oligo-iduronic acid ligands (I34), which showed strong binding to the HB-EGF receptor over FGF2, and regulated EGF receptor-mediated cancer cell homing in both 2D and 3D cell culture systems. These findings provide a new practical imaging tool for carbohydrate research.
CHEMICAL COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Matthew J. Saunders, Robert J. Woods, Loretta Yang
Summary: The majority of mammalian proteins are glycosylated, with variations in protein glycosylation having significant effects on various biological activities. Monitoring and controlling protein glycosylation is crucial for ensuring the quality and consistency of therapeutic biologicals.
SCIENTIFIC REPORTS
(2023)
Article
Nanoscience & Nanotechnology
Preeti Ravindra Bhoge, Sandhya Mardhekar, Suraj Toraskar, Balamurugan Subramani, Raghavendra Kikkeri
Summary: This study demonstrates the synergistic effect of different shapes of gold nanoparticles (AuNPs) with toll-like receptor (TLR) agonists in immune modulation activity. It was found that rod-shaped AuNPs were taken up quickly but had poor immunogenic response, while star-shaped AuNPs exhibited intense pro-inflammatory cytokine secretion.
ACS APPLIED BIO MATERIALS
(2022)
Review
Chemistry, Multidisciplinary
Reagan J. J. Meredith, Ian Carmichael, Robert J. J. Woods, Anthony S. S. Serianni
Summary: The conformational properties of saccharides in solution have been difficult to characterize due to the complex nature of their structures and the limitations of NMR spectroscopy. Current methods heavily rely on theoretical calculations, such as molecular dynamics simulations, which are not ideal due to the lack of independent experimental validation. A recent development, MA'AT analysis, combines experimental and computational methods to provide accurate torsion angle distributions and overcome the limitations of current approaches.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Review
Chemistry, Medicinal
Preeti Ravindra Bhoge, Ankita Chandra, Raghavendra Kikkeri
Summary: Carbohydrate-protein interactions are crucial for regulating physiological and pathological processes. To enhance the avidity of these interactions, multivalent probes like nanoparticles and polymer scaffolds have been developed. The morphology of glyco-nanostructures also affects protein binding, bacterial adhesion, cellular internalization, and immune responses. This review focuses on the advancements in glyco-nanostructures of different shapes and their potential applications in glycobiology.
Article
Chemistry, Physical
Yao Xiao, Robert J. J. Woods
Summary: An empirical energy function based on quantum mechanical data was developed to describe the interaction between methane and benzene, including the contribution from CH-& pi; interactions. This interaction is frequently observed in protein-ligand crystal structures, but has been difficult to quantify. The addition of a CH-& pi; term to the AutoDock Vina (AD VINA) scoring function improved the prediction of the orientation of flexible ligands in protein-binding sites and enhanced the detection of carbohydrate-binding sites displaying CH-& pi; interactions. Furthermore, the docking performance for benchmark sets was also improved.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Biochemistry & Molecular Biology
Amanda L. Lewis, Philip Toukach, Evan Bolton, Xi Chen, Martin Frank, Thomas Luetteke, Yuriy Knirel, Ian Schoenhofen, Ajit Varki, Evgeny Vinogradov, Robert J. Woods, Natasha Zachara, Jian Zhang, Johannis P. Kamerling, Sriram Neelamegham
Summary: Nonulosonic acids, also known as NulOs, are a group of 2-ketoaldonic acids with a 9-carbon backbone. They occur in two forms in nature, namely the 3-deoxy sialic acids in deuterostomes like vertebrates and their pathogens, and the 3,9-dideoxy sialic-acid-like molecules found in bacteria and archaea. NulOs play significant roles in evolution, biology, and disease, and their diversity is reflected in over 90 sialic acid forms and 50 sialic-acid-like variants.
Meeting Abstract
Biochemistry & Molecular Biology
Sheng-Cheng Wu, Christian Gerner-Smidt, Lu Meng, Shaza Abnouf, Robert J. Woods, Loretta Yang
Meeting Abstract
Biochemistry & Molecular Biology
Yao Xiao, Alyssa Wright, Sawsan Mahmoud, Daniel Wentworth, Robert J. Woods
