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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..

A sulphated glycosaminoglycan extract from Placopecten magellanicus inhibits the Alzheimer's disease ß-site amyloid precursor protein cleaving enzyme 1 (BACE-1). (2023)
Journal Article
Mycroft-West, C., Devlin, A., Cooper, L., Guimond, S., Procter, P., Miller, G., …Skidmore, M. (2023). A sulphated glycosaminoglycan extract from Placopecten magellanicus inhibits the Alzheimer's disease ß-site amyloid precursor protein cleaving enzyme 1 (BACE-1). Carbohydrate Research, 525, Article 108747. https://doi.org/10.1016/j.carres.2023.108747

The clinically important anticoagulant heparin, a member of the glycosaminoglycan family of carbohydrates that is extracted predominantly from porcine and bovine tissue sources, has previously been shown to inhibit the ß-site amyloid precursor protei... Read More about A sulphated glycosaminoglycan extract from Placopecten magellanicus inhibits the Alzheimer's disease ß-site amyloid precursor protein cleaving enzyme 1 (BACE-1)..

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..

The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models. (2021)
Journal Article
Davies, S., Mycroft-West, C., Pagani, I., Hill, H., Chen, Y., Karlsson, R., …Richardson, A. (2021). The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models. Frontiers in Pharmacology, 12, 660490. https://doi.org/10.3389/fphar.2021.660490

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the di... Read More about The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models..

Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease ß Secretase, BACE1 (2021)
Journal Article
Mycroft-West, C. J., Devlin, A. J., Cooper, L. C., Guimond, S. E., Procter, P., Guerrini, M., …Skidmore, M. A. (2021). Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease ß Secretase, BACE1. Marine Drugs, 19(4), 203 -203. https://doi.org/10.3390/md19040203

Only palliative therapeutic options exist for the treatment of Alzheimer’s Disease; no new successful drug candidates have been developed in over 15 years. The widely used clinical anticoagulant heparin has been reported to exert beneficial effects t... Read More about Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease ß Secretase, BACE1.

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..

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.

Inhibition of BACE1, the ß-secretase implicated in Alzheimer's disease, by a chondroitin sulfate extract from Sardina pilchardus. (2020)
Journal Article
Mycroft-West, C. J., Devlin, A. J., Cooper, L. C., Procter, P., Miller, G. J., Fernig, D. G., …Skidmore, M. A. (2020). Inhibition of BACE1, the ß-secretase implicated in Alzheimer's disease, by a chondroitin sulfate extract from Sardina pilchardus. Neural Regeneration Research, 15(8), 1546 - 1553. https://doi.org/10.4103/1673-5374.274341

The pharmaceutical and anticoagulant agent heparin, a member of the glycosaminoglycan family of carbohydrates, has previously been identified as a potent inhibitor of a key Alzheimer's disease drug target, the primary neuronal ß-secretase, ß-site amy... Read More about Inhibition of BACE1, the ß-secretase implicated in Alzheimer's disease, by a chondroitin sulfate extract from Sardina pilchardus..

Tools for the Quality Control of Pharmaceutical Heparin. (2019)
Journal Article
Devlin, A., Mycroft-West, C., Procter, P., Cooper, L., Guimond, S., Andrade De Lima, M., …Skidmore, M. (2019). Tools for the Quality Control of Pharmaceutical Heparin. Medicina, 55, 636 - 636. https://doi.org/10.3390/medicina55100636

Heparin is a vital pharmaceutical anticoagulant drug and remains one of the few naturally sourced pharmaceutical agents used clinically. Heparin possesses a structural order with up to four levels of complexity. These levels are subject to change bas... Read More about Tools for the Quality Control of Pharmaceutical Heparin..

A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer's Disease. (2019)
Journal Article
Mycroft-West, C., Cooper, L., Devlin, A., Procter, P., Guimond, S., Guerrini, M., …Skidmore, M. (2019). A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer's Disease. Marine Drugs, 17, 293 -293. https://doi.org/10.3390/md17050293

Therapeutic options for Alzheimer's disease, the most common form of dementia, are currently restricted to palliative treatments. The glycosaminoglycan heparin, widely used as a clinical anticoagulant, has previously been shown to inhibit the Alzheim... Read More about A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer's Disease..

Variations in the Peritrophic Matrix Composition of Heparan Sulphate from the Tsetse Fly, Glossina morsitans morsitans (2018)
Journal Article
Rogerson, E., Pelletier, J., Acosta-Serrano, A., Rose, C., Taylor, S., Guimond, S., …Yates, E. (2018). Variations in the Peritrophic Matrix Composition of Heparan Sulphate from the Tsetse Fly, Glossina morsitans morsitans. Pathogens an international, open access journal of pathogens and pathogen-host interactions, 7, https://doi.org/10.3390/pathogens7010032

Tsetse flies are the principal insect vectors of African trypanosomes-sleeping sickness in humans and Nagana in cattle. One of the tsetse fly species, Glossina morsitans morsitans, is host to the parasite, Trypanosoma brucei, a major cause of African... Read More about Variations in the Peritrophic Matrix Composition of Heparan Sulphate from the Tsetse Fly, Glossina morsitans morsitans.

A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence (2017)
Journal Article
Skidmore, M., Mohd Fadzli Mustaffa, K., Cooper, L. C., Guimond, S. E., Yates, E. A., & Craig, A. G. (2017). A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence. PloS one, 12(10), Article e0186276. https://doi.org/10.1371/journal.pone.0186276

A feature of mature Plasmodium falciparum parasitized red blood cells is their ability to bind surface molecules of the microvascular endothelium via the parasite-derived surface protein Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).... Read More about A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence.

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..