Review
Cell Biology
Jian Liu, Lars C. Pedersen
Summary: This article summarizes the recent progress in substrate specificity studies of different 3-O-sulfotransferase isoforms and introduces a newly developed method for analyzing the level of 3-O-sulfated heparan sulfate using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Samuel G. Holmes, Umesh R. Desai
Summary: Although molecular docking remains challenging for glycosaminoglycans (GAGs) due to their flexibility and anionic character, using a semi-rigid docking protocol can better reproduce the native topology of heparin/heparan sulfate (Hp/HS). Rigid and semi-rigid protocols are more accurate in predicting longer chain poses, while the semi-rigid approach is better for 2-4-mer poses. The new semi-rigid protocol, combined with a new computational parameter, shows promising potential for high-throughput screening of GAG sequences and identifying drug targets and drug-like Hp/HS sequences.
Article
Chemistry, Multidisciplinary
Imlirenla Pongener, Conor O'Shea, Hannah Wootton, Michael Watkinson, Gavin J. Miller
Summary: This review focuses on the chemical approaches and methodology improvements for the synthesis of heparin and heparan sulfate since 2015, including advances in accessing the pentasaccharide anticoagulant and targets for heparan sulfate synthesis. It also discusses key building block synthesis, oligosaccharide construction, chemical sulfation techniques, and technological improvements to traditional solution-phase synthesis approaches.
Article
Biochemistry & Molecular Biology
Jesper Bergwik, Amanda Kristiansson, Jorgen Larsson, Simon Ekstrom, Bo Akerstrom, Maria Allhorn
Summary: A1M can bind to heparin and HS, and can be purified from human plasma using heparin affinity chromatography and size exclusion chromatography. The binding strength is inversely proportional to salt concentration and directly proportional to the sulfation degree of heparin and HS.
Article
Biochemistry & Molecular Biology
Angela Boyce, Gary Walsh
Summary: Heparinases are enzymes that selectively cleave heparin and heparan sulfate chains, with potential therapeutic applications in cancer treatment, inhibition of neovascularization, and other biological processes. Their industrial and clinical significance has been underscored by their ability to produce low molecular weight heparin and neutralize heparin in blood.
Review
Biochemistry & Molecular Biology
Mingjia Yu, Tianji Zhang, Wei Zhang, Qianyun Sun, Hongmei Li, Jin-ping Li
Summary: The infectious disease caused by SARS-CoV-2 has become a major threat with high mortality rates and rapid spread, leading to over 70 million infections and 1.6 million deaths. New strategies are urgently needed for treatment due to the lack of effective therapeutics or widely available vaccines. The use of heparin/HS and their mimetics may serve as potential drugs by competing with cell surface HS to prevent viral adhesion and modulate inflammatory reactions, highlighting the importance of understanding coronavirus invasion mechanisms and HS-protein interactions for potential treatment avenues.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Bryan E. Thacker, Kristen J. Thorne, Colin Cartwright, Jeeyoung Park, Kimberly Glass, Annie Chea, Benjamin P. Kellman, Nathan E. Lewis, Zhenping Wang, Anna Di Nardo, Susan T. Sharfstein, Walter Jeske, Jeanine Walenga, John Hogwood, Elaine Gray, Barbara Mulloy, Jeffrey D. Esko, Charles A. Glass
Summary: Heparin, an essential anticoagulant, is currently sourced from vulnerable animal populations. This study demonstrates the feasibility of producing high anticoagulant potency heparin sulfate through genome engineering in cell culture, providing a potential alternative to animal sources.
METABOLIC ENGINEERING
(2022)
Review
Biochemistry & Molecular Biology
Yi-En Liao, Jian Liu, Katelyn Arnold
Summary: Heparan sulfates and heparan sulfate binding proteins play crucial roles in regulating vascular homeostasis and host response in sepsis. Dysregulation of these molecules can exacerbate inflammation and coagulation. Understanding the structure-function relationship between heparan sulfates and heparan sulfate binding proteins is essential for drug development and potential therapeutic interventions in sepsis.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Ariel J. Ben-Sasson, Joseph L. Watson, William Sheffler, Matthew Camp Johnson, Alice Bittleston, Logeshwaran Somasundaram, Justin Decarreau, Fang Jiao, Jiajun Chen, Ioanna Mela, Andrew A. Drabek, Sanchez M. Jarrett, Stephen C. Blacklow, Clemens F. Kaminski, Greg L. Hura, James J. De Yoreo, Justin M. Kollman, Hannele Ruohola-Baker, Emmanuel Derivery, David Baker
Summary: By designing rigid interfaces, we have successfully generated binary layers co-assembled by two protein components, and experiments have shown that this material can rapidly form ordered structures in vitro and in cells. This design approach allows for customization and symmetry reconfiguration, enabling the formation of ligand arrays that can drive receptor clustering, downstream protein recruitment, and signaling.
Article
Biochemistry & Molecular Biology
Lauren A. Gandy, Ashley J. Canning, Huan Lou, Ke Xia, Peng He, Guowei Su, Tina Cairns, Jian Liu, Fuming Zhang, Robert J. Linhardt, Gary Cohen, Chunyu Wang
Summary: This study investigates the interaction between glycoprotein D (gD) and neuronal surface glycan heparan sulfate (HS) from both the protein and glycan perspective. The results reveal that the N-terminal region of gD is not crucial for heparin binding, while the conformational dynamics of the C-terminal region modulate the receptor binding. Additionally, gD shows a strong preference for 6-O-sulfate and the importance of 2-O-sulfation increases in the presence of 6-O-S.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Immunology
Yanmei Hu, Xiangzhi Meng, Fushun Zhang, Yan Xiang, Jun Wang
Summary: The study highlights the important role of HSPGs in SARS-CoV-2 cell attachment, and demonstrates the broad-spectrum antiviral activity of LF against various coronaviruses, especially with BLF being more potent than HLF. BLF binds to HSPGs to block viral attachment, and its antiviral activity can be antagonized by the HSPG mimetic heparin. Combination therapy experiment shows synergistic effect of LF with remdesivir in cell culture.
EMERGING MICROBES & INFECTIONS
(2021)
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.
Review
Biochemistry & Molecular Biology
Johannes Gottschalk, Lothar Elling
Summary: Glycosaminoglycans (GAGs) are linear anionic polysaccharides with specific sulfation patterns, and recent research has focused on tailored production strategies and enzyme cascades to overcome challenges such as contamination and uncontrolled sulfation patterns. Despite advancements in chemoenzymatic synthesis, the complex production of GAGs remains a challenging field of research.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Alba Monferrer, Jessica A. Kretzmann, Christian Sigl, Pia Sapelza, Anna Liedl, Barbara Wittmann, Hendrik Dietz
Summary: This study reports a virus encapsulation platform based on DNA origami structures that can effectively trap a broad range of viruses by exploiting the affinity and attachment of viruses to heparan sulfate proteoglycans. The DNA origami shells can encapsulate multiple virus particles and prevent further interactions with cell surface receptors.
Article
Chemistry, Multidisciplinary
Katerina Brodsky, Kristyna Kanova, Dorota Konvalinkova, Kristyna Slamova, Helena Pelantova, Katerina Valentova, Pavla Bojarova, Vladimir Kren, Lucie Petraskova
Summary: Enzymatic sulfation is an important and understudied topic, and finding suitable sulfate donors is a major challenge. This study investigated the impact of different sulfate donors on enzyme-catalyzed sulfation, and evaluated the sulfated compounds obtained.