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..

Synthesis of fluorinated carbocyclic pyrimidine nucleoside analogues (2022)
Journal Article
Benckendorff, C., Slyusarchuk, V. D., Huang, N., Lima, M. A., Smith, M., & Miller, G. J. (2022). Synthesis of fluorinated carbocyclic pyrimidine nucleoside analogues. Organic and Biomolecular Chemistry, 20(47), 9469 - 9489. https://doi.org/10.1039/D2OB01761J

Analogues of the canonical nucleosides have a longstanding presence and proven capability within medicinal chemistry and drug discovery research. The synthesis reported herein successfully replaces furanose oxygen with CF2 and CHF in pyrimidine nucle... Read More about Synthesis of fluorinated carbocyclic pyrimidine nucleoside analogues.

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.

Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate. (2022)
Journal Article
Meneghetti, M., Naughton, L., O'Shea, C., Koffi Teki, D., Chagnault, V., Nader, H., …Andrade De Lima, M. (2022). Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate. ACS Omega, 7(28), 24461 - 24467. https://doi.org/10.1021/acsomega.2c02070

Heparan sulfate (HS), a sulfated linear carbohydrate that decorates the cell surface and extracellular matrix, is ubiquitously distributed throughout the animal kingdom and represents a key regulator of biological processes and a largely untapped res... Read More about Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate..

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.

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.

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.

A Further Unique Chondroitin Sulfate from the shrimp Litopenaeus vannamei with Antithrombin Activity that Modulates Acute Inflammation (2019)
Journal Article
Palhares, L., Brito, A., Andrade De Lima, M., Nader, H., London, J., Barsukov, I., …Chavante, S. (2019). A Further Unique Chondroitin Sulfate from the shrimp Litopenaeus vannamei with Antithrombin Activity that Modulates Acute Inflammation. Carbohydrate Polymers, 115031--115031. https://doi.org/10.1016/j.carbpol.2019.115031

The detailed structure of a further Chondroitin Sulfate from Litopenaeus vannamei shrimp (sCS) is described. The backbone structure was established by 1H/13C NMR, which identified 3-O-sulfated GlcA, 4-O-sulfated GalNAc, 6-O-sulfated GalNAc, and 4,6-d... Read More about A Further Unique Chondroitin Sulfate from the shrimp Litopenaeus vannamei with Antithrombin Activity that Modulates Acute Inflammation.

Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants (2019)
Journal Article
Mendes, A., Meneghetti, M., Palladino, M., Justo, G., Sassaki, G., Fareed, J., …Nader, H. (2019). Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants. Molecules, 24, 2988--2988. https://doi.org/10.3390/molecules24162988

Nowadays, pharmaceutical heparin is purified from porcine and bovine intestinal mucosa. In the past decade there has been an ongoing concern about the safety of heparin, since in 2008, adverse effects associated with the presence of an oversulfated c... Read More about Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants.

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..

Subverting the mechanisms of cell death: flavivirus manipulation of host cell responses to infection (2018)
Journal Article
Vicenzi, E., Pagani, I., Ghezzi, S., Taylor, S. L., Rudd, T. R., Lima, M. A., …Yates, E. A. (2018). Subverting the mechanisms of cell death: flavivirus manipulation of host cell responses to infection. Biochemical Society Transactions, 46, 609-617. https://doi.org/10.1042/BST20170399

Viruses exploit host metabolic and defence machinery for their own replication. The flaviviruses, which include Dengue (DENV), Yellow Fever (YFV), Japanese Encephalitis (JEV), West Nile (WNV) and Zika (ZIKV) viruses, infect a broad range of hosts, ce... Read More about Subverting the mechanisms of cell death: flavivirus manipulation of host cell responses to infection.

19 F labelled glycosaminoglycan probes for solution NMR and non-linear (CARS) microscopy (2016)
Journal Article
Lima, M. A., Cavalheiro, R. P., Viana, G. M., Meneghetti, M. C., Rudd, T. R., Skidmore, M., …Yates, E. A. (2016). 19 F labelled glycosaminoglycan probes for solution NMR and non-linear (CARS) microscopy. Glycoconjugate Journal, 34, 405-410. https://doi.org/10.1007/s10719-016-9723-x

Studying polysaccharide-protein interactions under physiological conditions by conventional techniques is challenging. Ideally, macromolecules could be followed by both in vitro spectroscopy experiments as well as in tissues using microscopy, to enab... Read More about 19 F labelled glycosaminoglycan probes for solution NMR and non-linear (CARS) microscopy.