A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer's Disease.

Mycroft-West, CJ; Cooper, LC; Devlin, AJ; Procter, P; Guimond, SE; Guerrini, M; Fernig, DG; Lima, MA; Yates, EA; Skidmore, MA

doi:10.3390/md17050293

Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1 (2024)
Journal Article
Mycroft-West, C. J., Abdelkarim, S., Duyvesteyn, H. M. E., Gandhi, N. S., Skidmore, M. A., Owens, R. J., & Wu, L. (in press). Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1. Nature Communications, 15(1), Article 1326. https://doi.org/10.1038/s41467-024-45419-4

Heparan sulfate (HS) polysaccharides are major constituents of the extracellular matrix, which are involved in myriad structural and signaling processes. Mature HS polysaccharides contain complex, non-templated patterns of sulfation and epimerization... Read More about Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1.

Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides (2023)
Journal Article
Wahart, A. J. C., Dolan, J. P., Anderson, S. D., Cheallaigh, A. N., Staniland, J., Lima, M. A., …Cosgrove, S. C. (2023). Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides. ChemBioChem, Article e202300752. https://doi.org/10.1002/cbic.202300752

Wahart et al. demonstrate the use of an immobilised oxidase enzyme coupled to an extractive amino resin for the bioremediation of a common industrial surfactant. This allows the facile purification of alkyl monoglucosides without the need for high en... Read More about Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides.

Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides. (2023)
Journal Article
Wahart, A. J. C., Dolan, J. P., Anderson, S. D., Cheallaigh, A. N., Staniland, J., Lima, M. A., …Cosgrove, S. C. (in press). Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides. ChemBioChem, Article e202300625. https://doi.org/10.1002/cbic.202300625

As the world moves towards net-zero carbon emissions, the development of sustainable chemical manufacturing processes is essential. Within manufacturing, purification by distillation is often used, however this process is energy intensive and methods... Read More about Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides..

Virtual screening, identification and in vitro validation of small molecule GDP-mannose dehydrogenase inhibitors † (2023)
Journal Article
Dolan, J., Ahmadipour, S., Wahart, A., Ni Cheallaigh, A., Sari, S., Eurtivong,, C., …Miller, G. (2023). Virtual screening, identification and in vitro validation of small molecule GDP-mannose dehydrogenase inhibitors †. RSC Chemical Biology, 4(11), 865-870. https://doi.org/10.1039/D3CB00126A

Upon undergoing mucoid conversion within the lungs of cystic fibrosis patients, the pathogenic bacterium Pseudomonas aeruginosa synthesises copious quantities of the virulence factor and exopolysaccharide alginate. The enzyme guanosine diphosphate ma... Read More about Virtual screening, identification and in vitro validation of small molecule GDP-mannose dehydrogenase inhibitors †.

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..

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)..

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..

Analysis of protein-heparin interactions using a portable SPR instrument (2022)
Journal Article
Su, D., Li, Y., Yates, E., Skidmore, M., Andrade De Lima, M., & Fernig, D. (2022). Analysis of protein-heparin interactions using a portable SPR instrument. PeerJ Analytical Chemistry, 4, 1-16. https://doi.org/10.7717/peerj-achem.15

Optical biosensors such as those based on surface plasmon resonance (SPR) are a key analytical tool for understanding biomolecular interactions and function as well as the quantitative analysis of analytes in a wide variety of settings. The advent of... Read More about Analysis of protein-heparin interactions using a portable SPR instrument.

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..

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.

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..

Development of a nano-luciferase based assay to measure the binding of SARS-CoV-2 spike receptor binding domain to ACE-2 (2020)
Journal Article
Andrade De Lima, M., Skidmore, M., Khanim, F., & Richardson, A. (2020). Development of a nano-luciferase based assay to measure the binding of SARS-CoV-2 spike receptor binding domain to ACE-2. Biochemical and Biophysical Research Communications, 534, 485--490. https://doi.org/10.1016/j.bbrc.2020.11.055

To identify drugs that could potentially be used to treat infection with SARS-CoV-2, a high throughput 384-well assay was developed to measure the binding of the receptor binding domain (RBD) of the viral S1 protein to its main receptor, angiotensin... Read More about Development of a nano-luciferase based assay to measure the binding of SARS-CoV-2 spike receptor binding domain to ACE-2.

Molecular Changes in Dengue Envelope Protein Domain III upon Interaction with Glycosaminoglycans. (2020)
Journal Article
Hyatt, J. G., Prévost, S., Devos, J. M., Mycroft-West, C. J., Skidmore, M. A., & Winter, A. (2020). Molecular Changes in Dengue Envelope Protein Domain III upon Interaction with Glycosaminoglycans. Pathogens an international, open access journal of pathogens and pathogen-host interactions, 9(11), Article 935. https://doi.org/10.3390/pathogens9110935

Dengue fever is a rapidly emerging vector-borne viral disease with a growing global burden of approximately 390 million new infections per annum. The Dengue virus (DENV) is a flavivirus spread by female mosquitos of the aedes genus, but the mechanism... Read More about Molecular Changes in Dengue Envelope Protein Domain III upon Interaction with Glycosaminoglycans..

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..

All Outputs (33)