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Gavin Miller's Outputs (90)

Developments in the Chemical Synthesis of Heparin and Heparan Sulfate (2021)
Journal Article
Pongener, I., O'Shea, C., Wootton, H., Watkinson, M., & Miller, G. J. (2021). Developments in the Chemical Synthesis of Heparin and Heparan Sulfate. Chemical Record, 21(11), 3238-3255. https://doi.org/10.1002/tcr.202100173

Heparin and heparan sulfate represent key members of the glycosaminoglycan family of carbohydrates and underpin considerable repertoires of biological importance. As such, their efficiency of synthesis represents a key requirement, to further underst... Read More about Developments in the Chemical Synthesis of Heparin and Heparan Sulfate.

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate (2021)
Journal Article
Dimitriou, E., & Miller, G. (2021). Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate. Beilstein Journal of Organic Chemistry, 1527 - 1532. https://doi.org/10.3762/bjoc.17.110

<jats:p>Alginate is a biocompatible and industrially relevant polysaccharide that derives many of its important properties from the charged carboxylate groups within its polyuronic acid backbone. The design and inclusion of isosteric replacements for... Read More about Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate.

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..

Inhibition of the GDP-d-Mannose Dehydrogenase from Pseudomonas aeruginosa Using Targeted Sugar Nucleotide Probes (2020)
Journal Article
Beswick, L., Dimitriou, E., Ahmadipour, S., Zafar, A., Rejzek, M., Reynisson, J., …Miller, G. (2020). Inhibition of the GDP-d-Mannose Dehydrogenase from Pseudomonas aeruginosa Using Targeted Sugar Nucleotide Probes. ACS chemical biology, 15(12), 3086–3092. https://doi.org/10.1021/acschembio.0c00426

Sufferers of cystic fibrosis are at extremely high risk for contracting chronic lung infections. Over their lifetime, one bacterial strain in particular, Pseudomonas aeruginosa, becomes the dominant pathogen. Bacterial strains incur loss-of-function... Read More about Inhibition of the GDP-d-Mannose Dehydrogenase from Pseudomonas aeruginosa Using Targeted Sugar Nucleotide Probes.

Illuminating glycoscience: synthetic strategies for FRET-enabled carbohydrate active enzyme probes (2020)
Journal Article
Singh, M., Watkinson, M., Scanlan, E. M., & Miller, G. (2020). Illuminating glycoscience: synthetic strategies for FRET-enabled carbohydrate active enzyme probes. RSC Chemical Biology, 5(1), 352 - 368

Carbohydrates are synthesised, refined and degraded by carbohydrate active enzymes. FRET is emerging as a powerful tool to monitor and quantify their activity as well as to test inhibitors as new drug candidates and monitor disease.

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.

Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues. (2020)
Journal Article
Guinan, M., Benckendorff, C., Smith, M., & Miller, G. (2020). Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues. Molecules, 25(9), https://doi.org/10.3390/molecules25092050

Nucleoside analogues have proven to be highly successful chemotherapeutic agents in the treatment of a wide variety of cancers. Several such compounds, including gemcitabine and cytarabine, are the go-to option in first-line treatments. However, thes... Read More about Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues..

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..

Synthesis and Isolation of Diastereomeric Anomeric Sulfoxides from a d-Mannuronate Thioglycoside Building Block (2020)
Journal Article
Dimitriou, E., & Miller, G. (2020). Synthesis and Isolation of Diastereomeric Anomeric Sulfoxides from a d-Mannuronate Thioglycoside Building Block. Molbank, 2020(1), M1111. https://doi.org/10.3390/M1111

Methyl [S-phenyl 4-O-acetyl-2,3-di-O-benzyl-1-thio-&alpha;-d-mannopyranoside (R/S)S-oxide] uronate was synthesised from a thioglycoside mannosyl uronate donor in a 98% yield. By using one equivalent of meta-chloroperbenzoic acid (m-CPBA) as the sulph... Read More about Synthesis and Isolation of Diastereomeric Anomeric Sulfoxides from a d-Mannuronate Thioglycoside Building Block.

Exploring a glycosylation methodology for the synthesis of hydroxamate-modified alginate building blocks (2019)
Journal Article
Dimitriou, E., & Miller, G. (2019). Exploring a glycosylation methodology for the synthesis of hydroxamate-modified alginate building blocks. Organic and Biomolecular Chemistry, 17(42), 9321-9335. https://doi.org/10.1039/c9ob02053e

Alginate, an anionic polysaccharide, is an important industrial biomaterial naturally harvested from seaweed. Many of its important physicochemical properties derive from the presence of charged carboxylate groups presented as uronic acids within the... Read More about Exploring a glycosylation methodology for the synthesis of hydroxamate-modified alginate building blocks.

Chemical and enzymatic synthesis of the alginate sugar nucleotide building block: GDP-d-mannuronic acid (2019)
Journal Article
Beswick, L., Ahmadipour, S., Dolan, J. P., Rejzek, M., Field, R. A., & Miller, G. J. (2019). Chemical and enzymatic synthesis of the alginate sugar nucleotide building block: GDP-d-mannuronic acid. Carbohydrate Research, 485(1), 107819 -107819. https://doi.org/10.1016/j.carres.2019.107819

Highlights

Sugarnucleotide synthesis.

Chemical and enzymatic access to GDP-d-ManA.

Evaluation of protected and free uronate 1-phosphates for pyrophosphorylation.

6R/S-deutero-a-d-mannopyranoside 1-phosphate (2019)
Journal Article
Miller, G., & Ahmadipour, S. (2019). 6R/S-deutero-a-d-mannopyranoside 1-phosphate. Molbank, 2019(3), Article M1068. https://doi.org/10.3390/M1068

6R/S-deutero-a-d-mannopyranoside 1-phosphate was synthesised from a C6 aldehydic mannose thioglycoside donor in four steps. Using NaBD4 as the reductant, isotopic enrichment at C6 was achieved and the resultant C6-deuterated material was converted th... Read More about 6R/S-deutero-a-d-mannopyranoside 1-phosphate.

Chemoenzymatic Synthesis of C6-Modified Sugar Nucleotides To Probe the GDP-d-Mannose Dehydrogenase from Pseudomonas aeruginosa (2019)
Journal Article
Ahmadipour, S., Pergolizzi, G., Rejzek, M., Field, R. A., & Miller, G. J. (2019). Chemoenzymatic Synthesis of C6-Modified Sugar Nucleotides To Probe the GDP-d-Mannose Dehydrogenase from Pseudomonas aeruginosa. Organic Letters, 21(12), 4415-4419. https://doi.org/10.1021/acs.orglett.9b00967

The chemoenzymatic synthesis of a series of C6-modified GDP-d-Man sugar nucleotides is described. This provides the first structure–function tools for the GDP-d-ManA producing GDP-d-mannose dehydrogenase (GMD) from Pseudomonas aeruginosa. Using a com... Read More about Chemoenzymatic Synthesis of C6-Modified Sugar Nucleotides To Probe the GDP-d-Mannose Dehydrogenase from Pseudomonas aeruginosa.