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Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial (2024)
Journal Article
Ramos da Silva Grillo, V. T., Bertanha, M., da Silva Rodrigues, L., de Lima, M. A., Mellucci Filho, P. L., Rahal Guaragna Machado, R., …Fortaleza, C. M. C. B. (in press). Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial. Scientific Reports, 14(1), Article 19902. https://doi.org/10.1038/s41598-024-70064-8

To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evol... Read More about Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial.

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..

History and Prospects for the Sustainability and Circularity of the Windowpane Oyster Placuna placenta Fishery in the Philippines (2023)
Journal Article
Rustia, J. M., Antonino, J. P., Velasco, R. R., Lima, M. A., Yates, E. A., & Fernig, D. G. (in press). History and Prospects for the Sustainability and Circularity of the Windowpane Oyster Placuna placenta Fishery in the Philippines. Fishes, 8(10), Article 493. https://doi.org/10.3390/fishes8100493

The windowpane oyster Placuna placenta lives in brackish coastal waters and has long been economically important to the Philippines because of its durable and translucent shell, which is used as a glass substitute and material for making windowpanes... Read More about History and Prospects for the Sustainability and Circularity of the Windowpane Oyster Placuna placenta Fishery in the Philippines.

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..

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)..

Synthesis of 4-thio-d-glucopyranose and interconversion to 4-thio-d-glucofuranose. (2023)
Journal Article
Porter, J., Lima, M. A., Pongener, I., & Miller, G. (2023). Synthesis of 4-thio-d-glucopyranose and interconversion to 4-thio-d-glucofuranose. Carbohydrate Research, 524, Article 108759. https://doi.org/10.1016/j.carres.2023.108759

Sulfur containing glycosides offer an exciting prospect for inclusion within noncanonical glycan sequences, particularly as enabling probes for chemical glycobiology and for carbohydrate-based therapeutic development. In this context, we required acc... Read More about Synthesis of 4-thio-d-glucopyranose and interconversion to 4-thio-d-glucofuranose..

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..

Phosphorylation and sulfation share a common biosynthetic pathway, but extend biochemical and evolutionary diversity of biological macromolecules in distinct ways (2022)
Journal Article
Andrade De Lima, M., Rudd, T., Fernig, D., & Yates, E. (2022). Phosphorylation and sulfation share a common biosynthetic pathway, but extend biochemical and evolutionary diversity of biological macromolecules in distinct ways. Journal of the Royal Society. Interface, 19(193), https://doi.org/10.1098/rsif.2022.0391

<jats:p>Phosphate and sulfate groups are integral to energy metabolism and introduce negative charges into biological macromolecules. One purpose of such modifications is to elicit precise binding/activation of protein partners. The physico-chemical... Read More about Phosphorylation and sulfation share a common biosynthetic pathway, but extend biochemical and evolutionary diversity of biological macromolecules in distinct ways.

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

<jats:p>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 a... Read More about Analysis of protein-heparin interactions using a portable SPR instrument.

New anti-angiogenic compound based on chemically modified heparin (2022)
Journal Article
Kniggendorf, V., Souza, M., Russo, T., Andrade De Lima, M., Grupenmacher, A., Regatieri, C., & Dreyfuss, J. (2022). New anti-angiogenic compound based on chemically modified heparin. Graefe's Archive for Clinical and Experimental Ophthalmology, 1 - 9. https://doi.org/10.1007/s00417-022-05828-x

Purpose The purpose of this study was to measure the anti-angiogenic effect of N-desulfated Re–N-acetylated, a chemically modified heparin (mHep). Methods In vitro assays (cell tube formation, viability, proliferation, and migration) with endothelial... Read More about New anti-angiogenic compound based on chemically modified heparin.

Neuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation of Early Secretory Vesicle Transport (2022)
Journal Article
Moreira, D., Suzuki, A., Silva, A., Varella-Branco, E., Meneghetti, M., Kobayashi, G., …Passos-Bueno, M. (2022). Neuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation of Early Secretory Vesicle Transport. Frontiers in Cellular Neuroscience, 15, https://doi.org/10.3389/fncel.2021.803302

<jats:p>Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In thi... Read More about Neuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation of Early Secretory Vesicle Transport.

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..

Nebulized enriched heparin to treat no critical patients with Sars-Cov-2 (2021)
Journal Article
Bertanha, M., Rodrigues, L. D. S., Mellucci Filho, P. L., Moroz, A., Pardini, M. I. D. M. C., Sobreira, M. L., …Fortaleza, C. M. C. B. (in press). Nebulized enriched heparin to treat no critical patients with Sars-Cov-2. Medicine, 100(51), e28288. https://doi.org/10.1097/md.0000000000028288

Background: Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that spreads rapidly, reaching pandemic status, causing the collapse of numerous health systems, and a strong economic and social impact. The treatment so far has not been... Read More about Nebulized enriched heparin to treat no critical patients with Sars-Cov-2.

Chemical synthesis of 4'-thio and 4'-sulfinyl pyrimidine nucleoside analogues. (2021)
Journal Article
Guinan, M., Huang, N., Hawes, C. S., Lima, M. A., Smith, M., & Miller, G. J. (2021). Chemical synthesis of 4'-thio and 4'-sulfinyl pyrimidine nucleoside analogues. Organic and Biomolecular Chemistry, 20(7), 1401-1406. https://doi.org/10.1039/d1ob02097h

Analogues of the canonical nucleosides required for nucleic acid synthesis have a longstanding presence and proven capability within antiviral and anticancer research. 4'-Thionucleosides, that incorporate bioisosteric replacement of furanose oxygen w... Read More about Chemical synthesis of 4'-thio and 4'-sulfinyl pyrimidine nucleoside analogues..

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..

Endocytosis and the Participation of Glycosaminoglycans Are Important to the Mechanism of Cell Death Induced by β-Hairpin Antimicrobial Peptides (2021)
Journal Article
Buri, M. V., Sperandio, L. P., de Souza, K. F. S., Antunes, F., Rezende, M. M., Melo, C. M., …Paredes-Gamero, E. J. (2021). Endocytosis and the Participation of Glycosaminoglycans Are Important to the Mechanism of Cell Death Induced by β-Hairpin Antimicrobial Peptides. ACS Applied Biomaterials, 4(8), 6488--6501. https://doi.org/10.1021/acsabm.1c00390

The cytotoxic mode of action of four antimicrobial peptides (AMPs) (gomesin, tachyplesin, protegrin, and polyphemusin) against a HeLa cell tumor model is discussed. A study of cell death by AMP stimulation revealed some similarities, including annexi... Read More about Endocytosis and the Participation of Glycosaminoglycans Are Important to the Mechanism of Cell Death Induced by β-Hairpin Antimicrobial Peptides.