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Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1 (2024)
Journal Article

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.

Virtual screening, identification and in vitro validation of small molecule GDP-mannose dehydrogenase inhibitors † (2023)
Journal Article

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

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

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

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

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

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

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

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..

Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations. (2021)
Journal Article

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

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

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.

SARS-CoV-2 Spike S1 Receptor Binding Domain undergoes Conformational Change upon Interaction with Low Molecular Weight Heparins (2020)
Journal Article

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.

Inhibition of BACE1, the ß-secretase implicated in Alzheimer's disease, by a chondroitin sulfate extract from Sardina pilchardus. (2020)
Journal Article

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..

A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer's Disease. (2019)
Journal Article

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

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.

In vitro investigations on the effects of semi-synthetic, sulphated carbohydrates on the immune status of cultured common carp (Cyprinus carpio) leucocytes. (2017)
Journal Article

The rapid emergence of drug resistance, unfavourable immunosuppression and mounting evidence to suggest the deleterious accumulation of drug breakdown residues within animal tissues has driven a strong desire to move away from these current methods o... Read More about In vitro investigations on the effects of semi-synthetic, sulphated carbohydrates on the immune status of cultured common carp (Cyprinus carpio) leucocytes..

Identification of heparin modifications and polysaccharide inhibitors of Plasmodium falciparum merozoite invasion that have potential for novel drug development. (2017)
Journal Article

Despite recent successful control efforts, malaria remains a leading global health burden. Alarmingly, resistance to current antimalarials is increasing, and the development of new drug families is needed to maintain malaria control. Current antimala... Read More about Identification of heparin modifications and polysaccharide inhibitors of Plasmodium falciparum merozoite invasion that have potential for novel drug development..

The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding
Journal Article

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.