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Correction: Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes (2024)
Journal Article
Gamez, M., Elhegni, H. E., Fawaz, S., Ho Ho, K., Campbell, N. W., Copland, D. A., …Foster, R. R. (in press). Correction: Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes. Cardiovascular Diabetology, 23(1), 74. https://doi.org/10.1186/s12933-024-02170-w

Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes (2024)
Journal Article
Gamez, M., Elhegni, H. E., Fawaz, S., Ho, K. H., Campbell, N. W., Copland, D. A., …Foster, R. R. (in press). Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes. Cardiovascular Diabetology, 23(1), Article 50. https://doi.org/10.1186/s12933-024-02133-1

Background Diabetes mellitus is a chronic disease which is detrimental to cardiovascular health, often leading to secondary microvascular complications, with huge global health implications. Therapeutic interventions that can be applied to multiple... Read More about Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes.

Heparin Precursors with Reduced Anticoagulant Properties Retain Antiviral and Protective Effects that Potentiate the Efficacy of Sofosbuvir against Zika Virus Infection in Human Neural Progenitor Cells (2023)
Journal Article
Pagani, I., Ottoboni, L., Panina-Bordignon, P., Martino, G., Poli, G., Taylor, S., …Vicenzi, E. (in press). Heparin Precursors with Reduced Anticoagulant Properties Retain Antiviral and Protective Effects that Potentiate the Efficacy of Sofosbuvir against Zika Virus Infection in Human Neural Progenitor Cells. Pharmaceuticals, 16(10), Article 1385. https://doi.org/10.3390/ph16101385

Zika virus (ZIKV) infection during pregnancy can result in severe birth defects, such as microcephaly, as well as a range of other related health complications. Heparin, a clinical-grade anticoagulant, is shown to protect neural progenitor cells from... Read More about Heparin Precursors with Reduced Anticoagulant Properties Retain Antiviral and Protective Effects that Potentiate the Efficacy of Sofosbuvir against Zika Virus Infection in Human Neural Progenitor Cells.

Low sulfated heparan sulfate mimetic differentially affects repair in immune-mediated and toxin-induced experimental models of demyelination. (2023)
Journal Article
Turnbull. (2023). Low sulfated heparan sulfate mimetic differentially affects repair in immune-mediated and toxin-induced experimental models of demyelination. Glia, 71(7), 1683-1698. https://doi.org/10.1002/glia.24363

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... Read More about Low sulfated heparan sulfate mimetic differentially affects repair in immune-mediated and toxin-induced experimental models of demyelination..

Validation of Recombinant Heparan Sulphate Reagents for CNS Repair. (2023)
Journal Article
Turnbull. (2023). Validation of Recombinant Heparan Sulphate Reagents for CNS Repair. Biology, 12(3), Article 407. https://doi.org/10.3390/biology12030407

Therapies that target the multicellular pathology of central nervous system (CNS) disease/injury are urgently required. Modified non-anticoagulant heparins mimic the heparan sulphate (HS) glycan family and have been proposed as therapeutics for CNS r... Read More about Validation of Recombinant Heparan Sulphate Reagents for CNS Repair..

Analysis of Heparin Samples by Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy in the Solid State. (2023)
Journal Article
Devlin, A. J., Mycroft-West, C. J., Turnbull, J. E., Andrade De Lima, M., Guerrini, M., Yates, E. A., & Skidmore, M. A. (2023). Analysis of Heparin Samples by Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy in the Solid State. ACS Central Science, 9, 381-392. https://doi.org/10.1021/acscentsci.2c01176

Heparin is a polydisperse, heterogeneous polysaccharide of the glycosaminoglycan (GAG) class that has found widespread clinical use as a potent anticoagulant and is classified as an essential medicine by the World Health Organization. The importance... Read More about Analysis of Heparin Samples by Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy in the Solid State..

High sensitivity (zeptomole) detection of BODIPY- labelled heparan sulfate (HS) disaccharides by ion-paired RP-HPLC and LIF detection enables analysis of HS from mosquito midguts. (2023)
Journal Article
Maciej-Hulme, M. L., Leprince, A. C., Lavin, A., Guimond, S. E., Turnbull, J. E., Pelletier, J., …Skidmore, M. A. (2023). High sensitivity (zeptomole) detection of BODIPY- labelled heparan sulfate (HS) disaccharides by ion-paired RP-HPLC and LIF detection enables analysis of HS from mosquito midguts. Analytical Methods, 15(11), 1461-1469. https://doi.org/10.1039/d2ay01803a

The fine structure of heparan sulfate (HS), the glycosaminoglycan polysaccharide component of cell surface and extracellular matrix HS proteoglycans, coordinates the complex cell signalling processes that control homeostasis and drive development in... Read More about High sensitivity (zeptomole) detection of BODIPY- labelled heparan sulfate (HS) disaccharides by ion-paired RP-HPLC and LIF detection enables analysis of HS from mosquito midguts..

Chemokine CXCL4 interactions with extracellular matrix proteoglycans mediate widespread immune cell recruitment independent of chemokine receptors. (2023)
Journal Article
Gray, A., Karlsson, R., Roberts, A., Ridley, A., Pun, N., Khan, B., …Salanga, C. (2023). Chemokine CXCL4 interactions with extracellular matrix proteoglycans mediate widespread immune cell recruitment independent of chemokine receptors. Cell Reports, 111930 - ?. https://doi.org/10.1016/j.celrep.2022.111930

Leukocyte recruitment from the vasculature into tissues is a crucial component of the immune system but is also key to inflammatory disease. Chemokines are central to this process but have yet to be therapeutically targeted during inflammation due to... Read More about Chemokine CXCL4 interactions with extracellular matrix proteoglycans mediate widespread immune cell recruitment independent of chemokine receptors..

Evidence for multiple binding modes in the initial contact between SARS-CoV-2 spike S1 protein and cell surface glycans. (2022)
Journal Article
Parafioriti, M., Ni, M., Petitou, M., Mycroft‐West, C. J., Rudd, T. R., Gandhi, N. S., …Elli, S. (2023). Evidence for multiple binding modes in the initial contact between SARS-CoV-2 spike S1 protein and cell surface glycans. Chemistry - A European Journal, 29(1), https://doi.org/10.1002/chem.202202599

Infection of host cells by SARS-CoV-2 begins with recognition by the virus S (spike) protein of cell surface heparan sulfate (HS), tethering the virus to the extracellular matrix environment, and causing the subunit S1-RBD to undergo a conformational... Read More about Evidence for multiple binding modes in the initial contact between SARS-CoV-2 spike S1 protein and cell surface glycans..

Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction. (2022)
Journal Article
Guimond, S., Mycroft-West, C. J., Gandhi, N. S., Tree, J. A., C.Le, T. T., Spalluto, M., …Turnbull, J. E. (2022). Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction. ACS Central Science, 8(5), 527 - 545. https://doi.org/10.1021/acscentsci.1c01293

Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibi... Read More about Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction..

Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain. (2021)
Journal Article
Schuurs, Z. P., Hammond, E., Elli, S., Rudd, T. R., Mycroft-West, C. J., Lima, M. A., …Gandhi, N. S. (2021). Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain. Computational and Structural Biotechnology Journal, 19, 2806 - 2818. https://doi.org/10.1016/j.csbj.2021.05.002

SARS-CoV-2 has rapidly spread throughout the world's population since its initial discovery in 2019. The virus infects cells via a glycosylated spike protein located on its surface. The protein primarily binds to the angiotensin-converting enzyme-2 (... Read More about Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain..

Dissecting structure-function of 3-O-sulfated heparin and engineered heparan sulfates (2021)
Journal Article
Karlsson, R., Chopra, P., Joshi, A., Yang, Z., Vakhrushev, S. Y., Clausen, T. M., …Miller, R. L. (2021). Dissecting structure-function of 3-O-sulfated heparin and engineered heparan sulfates. Science Advances, 7(52), https://doi.org/10.1126/sciadv.abl6026

Heparan sulfate (HS) polysaccharides are master regulators of diverse biological processes via sulfated motifs that can recruit specific proteins. 3-O-sulfation of HS/heparin is crucial for anticoagulant activity, but despite emerging evidence for ro... Read More about Dissecting structure-function of 3-O-sulfated heparin and engineered heparan sulfates.

Tian-Huang Formula, a Traditional Chinese Medicinal Prescription, Improves Hepatosteatosis and Glucose Intolerance Targeting AKT-SREBP Nexus in Diet-Induced Obese Rats (2021)
Journal Article
Li, K., Yu, Y., Yuan, M., Zhang, C., Rong, X., Turnbull, J. E., & Guo, J. (2021). Tian-Huang Formula, a Traditional Chinese Medicinal Prescription, Improves Hepatosteatosis and Glucose Intolerance Targeting AKT-SREBP Nexus in Diet-Induced Obese Rats. Evidence-Based Complementary and Alternative Medicine, 2021, 1-15. https://doi.org/10.1155/2021/6617586

Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations. (2021)
Journal Article
Tree, J., Turnbull, J., Buttigieg, K., Elmore, M., Coombes, N., Hogwood, J., …Carroll, M. (2021). Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations. British Journal of Pharmacology, 178, 626--635. https://doi.org/10.1111/bph.15304

BACKGROUND AND PURPOSE: Currently, there are no licensed vaccines and limited antivirals for the treatment of COVID-19. Heparin (delivered systemically) is currently used to treat anticoagulant anomalies in COVID-19 patients. Additionally, in the Uni... Read More about Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations..

Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin. (2020)
Journal Article
Mycroft-West, C. J., Su, D., Pagani  , I., Rudd  , T. R., Elli  , S., Gandhi  , N. S., …Skidmore   , M. A. (2020). Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin. Thrombosis and Haemostasis, 120(12), 1700 - 1715. https://doi.org/10.1055/s-0040-1721319

The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means o... Read More about Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin..

Cryogenic Infrared Spectroscopy Reveals Structural Modularity in the Vibrational Fingerprints of Heparan Sulfate Diastereomers (2020)
Journal Article
Lettow, M., Grabarics, M., Greis, K., Mucha, E., Thomas, D. A., Chopra, P., …Pagel, K. (2020). Cryogenic Infrared Spectroscopy Reveals Structural Modularity in the Vibrational Fingerprints of Heparan Sulfate Diastereomers. Analytical Chemistry, 92(15), 10228-10232. https://doi.org/10.1021/acs.analchem.0c02048

Heparan sulfate and heparin are highly acidic polysaccharides with a linear sequence, consisting of alternating glucosamine and hexuronic acid building blocks. The identity of hexuronic acid units shows a variability along their sequence, as d-glucur... Read More about Cryogenic Infrared Spectroscopy Reveals Structural Modularity in the Vibrational Fingerprints of Heparan Sulfate Diastereomers.

Glycosaminoglycans induce conformational change in the SARS-CoV-2 Spike S1 Receptor Binding Domain (2020)
Journal Article
Mycroft-West, C. J., Su, D., Li, Y., Guimond, S. E., Rudd, T. R., Elli, S., …Skidmore, M. A. Glycosaminoglycans induce conformational change in the SARS-CoV-2 Spike S1 Receptor Binding Domain. bioRxiv, https://doi.org/10.1101/2020.04.29.068767

The glycosaminoglycan (GAG) class of polysaccharides are utilised by a plethora of microbial pathogens as receptors for adherence and invasion. The GAG heparin prevents infection by a range of viruses when added exogenously, including the S-associate... Read More about Glycosaminoglycans induce conformational change in the SARS-CoV-2 Spike S1 Receptor Binding Domain.

SARS-CoV-2 Spike S1 Receptor Binding Domain undergoes Conformational Change upon Interaction with Low Molecular Weight Heparins (2020)
Journal Article
Mycroft-West, C. J., Su, D., Li, Y., Guimond, S. E., Rudd, T. R., Elli, S., …Skidmore, M. A. SARS-CoV-2 Spike S1 Receptor Binding Domain undergoes Conformational Change upon Interaction with Low Molecular Weight Heparins. arXiv, https://doi.org/10.1101/2020.04.29.068486

The dependence of the host on the interaction of hundreds of extracellular proteins with the cell surface glycosaminoglycan heparan sulphate (HS) for the regulation of homeostasis is exploited by many microbial pathogens as a means of adherence and i... Read More about SARS-CoV-2 Spike S1 Receptor Binding Domain undergoes Conformational Change upon Interaction with Low Molecular Weight Heparins.

Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides (2020)
Journal Article
Miller, R. L., Guimond, S. E., Schwörer, R., Zubkova, O. V., Tyler, P. C., Xu, Y., …Pagel, K. (2020). Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides. Nature communications, 11, Article 1481. https://doi.org/10.1038/s41467-020-15284-y

Despite evident regulatory roles of heparan sulfate (HS) saccharides in numerous biological processes, definitive information on the bioactive sequences of these polymers is lacking, with only a handful of natural structures sequenced to date. Here,... Read More about Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides.

Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface. (2017)
Journal Article
Turnbull, & Guimond. (2017). Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface. Glia, 19 - 33. https://doi.org/10.1002/glia.23047

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cel... Read More about Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface..

Panels of chemically-modified heparin polysaccharides and natural heparan sulfate saccharides both exhibit differences in binding to Slit and Robo, as well as variation between protein binding and cellular activity (2016)
Journal Article
Ahmed, Y. A., Yates, E. A., Moss, D. J., Loeven, M. A., Hussain, S., Hohenester, E., …Powell, A. K. Panels of chemically-modified heparin polysaccharides and natural heparan sulfate saccharides both exhibit differences in binding to Slit and Robo, as well as variation between protein binding and cellular activity. Molecular BioSystems, 12(10), 3166-3175. https://doi.org/10.1039/c6mb00432f

Sulf1 and Sulf2 Differentially Modulate Heparan Sulfate Proteoglycan Sulfation during Postnatal Cerebellum Development: Evidence for Neuroprotective and Neurite Outgrowth Promoting Functions (2015)
Journal Article
Kalus, I., Rohn, S., Puvirajesinghe, T. M., Guimond, S. E., Eyckerman-Kölln, P. J., ten Dam, G., …Dierks, T. Sulf1 and Sulf2 Differentially Modulate Heparan Sulfate Proteoglycan Sulfation during Postnatal Cerebellum Development: Evidence for Neuroprotective and Neurite Outgrowth Promoting Functions. PloS one, 10(10), e0139853. https://doi.org/10.1371/journal.pone.0139853

Chemically modified, non-anticoagulant heparin derivatives are potent galectin-3 binding inhibitors and inhibit circulating galectin-3-promoted metastasis (2015)
Journal Article
Duckworth, C. A., Guimond, S. E., Sindrewicz, P., Hughes, A. J., French, N. S., Lian, L., …Yu, L. (2015). Chemically modified, non-anticoagulant heparin derivatives are potent galectin-3 binding inhibitors and inhibit circulating galectin-3-promoted metastasis. Oncotarget, 6(27), 23671-23687. https://doi.org/10.18632/oncotarget.4409

Composition, Sequencing and Ion Mobility Mass Spectrometry of Heparan Sulfate-like Octasaccharide Isomers Differing in Glucuronic and Iduronic Acid Content (2015)
Journal Article
Miller, R. L., Wei, W., Schwörer, R., Zubkova, O. V., Tyler, P. C., Turnbull, J. E., & Leary, J. A. (2015). Composition, Sequencing and Ion Mobility Mass Spectrometry of Heparan Sulfate-like Octasaccharide Isomers Differing in Glucuronic and Iduronic Acid Content. European Journal of Mass Spectrometry, 21(3), 245-254. https://doi.org/10.1255/ejms.1337

Synthesis of a Targeted Library of Heparan Sulfate Hexa- to Dodecasaccharides as Inhibitors of β-Secretase: Potential Therapeutics for Alzheimer’s Disease (2013)
Journal Article
Schwörer, R., Zubkova, O. V., Turnbull, J. E., & Tyler, P. C. (2013). Synthesis of a Targeted Library of Heparan Sulfate Hexa- to Dodecasaccharides as Inhibitors of β-Secretase: Potential Therapeutics for Alzheimer’s Disease. Chemistry - A European Journal, 19(21), 6817-6823. https://doi.org/10.1002/chem.201204519

The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding
Journal Article
Mycroft-West, C., Su, D., Elli, S., Li, Y., Guimond, S., Miller, G., …Skidmore, M. (2020). The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding. arXiv, https://doi.org/10.1101/2020.02.29.971093

Many pathogens take advantage of the dependence of the host on the interaction of hundreds of extracellular proteins with the glycosaminoglycans heparan sulphate to regulate homeostasis and use heparan sulphate as a means to adhere and gain access to... Read More about The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding.