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A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models. (2023)
Journal Article

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by the reduction of survival of motor neuron (SMN) protein levels. Although three SMN-augmentation therapies are clinically approved that significantly slow down disease progres... Read More about A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models..

Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manβ1,4GlcNAc library † (2023)
Journal Article

β-Mannosides are ubiquitous in nature, with diverse roles in many biological processes. Notably, Manβ1,4GlcNAc a constituent of the core N-glycan in eukaryotes was recently identified as an immune activator, highlighting its potential for use in immu... Read More about Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manβ1,4GlcNAc library †.

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 †.

Indolo[2,3- e ]benzazocines and indolo[2,3- f ]benzazonines and their copper( ii ) complexes as microtubule destabilizing agents † (2023)
Journal Article

A series of four indolo[2,3-e]benzazocines HL1–HL4 and two indolo[2,3-f]benzazonines HL5 and HL6, as well as their respective copper(ii) complexes 1–6, were synthesized and characterized by 1H and 13C NMR spectroscopy, ESI mass spectrometry, single c... Read More about Indolo[2,3- e ]benzazocines and indolo[2,3- f ]benzazonines and their copper( ii ) complexes as microtubule destabilizing agents †.

Chemical Diversification of Carbocyclic Fluorinated Pyrimidine Nucleosides: Introducing 2'-Arabino Analogues and Ring Unsaturation (2023)
Journal Article

Analogues of the canonical nucleosides have a longstanding presence and proven capability within medicinal chemistry and drug-discovery research. Herein, we report chemical diversification of carbocyclic pyrimidine nucleosides containing CF2 and CHF... Read More about Chemical Diversification of Carbocyclic Fluorinated Pyrimidine Nucleosides: Introducing 2'-Arabino Analogues and Ring Unsaturation.

Chemical synthesis of amphiphilic glycoconjugates: Access to amino, fluorinated and sulfhydryl oleyl glucosides. (2023)
Journal Article

Amphiphilic glycoconjugates offer an important prospect for development as chemical biology tools and biosurfactants. The chemical synthesis of such materials is required to expedite such prospect, compounded by the example of oleyl glycosides. Herei... Read More about Chemical synthesis of amphiphilic glycoconjugates: Access to amino, fluorinated and sulfhydryl oleyl glucosides..

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)..

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase. (2022)
Journal Article

Sufferers of cystic fibrosis are at significant risk of contracting chronic bacterial lung infections. The dominant pathogen in these cases is mucoid Pseudomonas aeruginosa. Such infections are characterised by overproduction of the exopolysaccharide... Read More about Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase..

Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate. (2022)
Journal Article

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..

Design, chemical synthesis and antiviral evaluation of 2'-deoxy-2'-fluoro-2'-C-methyl-4'-thionucleosides. (2022)
Journal Article

Nucleoside analogues represent an historically accomplished class of antiviral drug. Notwithstanding this, new molecular scaffolds are required to overcome their limitations and evolve pharmacophore space within this established field. Herein, we dev... Read More about Design, chemical synthesis and antiviral evaluation of 2'-deoxy-2'-fluoro-2'-C-methyl-4'-thionucleosides..

Chemical synthesis of C6-tetrazole ?-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate (2021)
Journal Article

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 these c... Read More about Chemical synthesis of C6-tetrazole ?-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate.

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..

Inhibition of the GDP-d-Mannose Dehydrogenase from Pseudomonas aeruginosa Using Targeted Sugar Nucleotide Probes (2020)
Journal Article

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.

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..

Synthesis and Isolation of Diastereomeric Anomeric Sulfoxides from a d-Mannuronate Thioglycoside Building Block (2020)
Journal Article

Methyl [S-phenyl 4-O-acetyl-2,3-di-O-benzyl-1-thio-α-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

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.

Chemoenzymatic Synthesis of C6-Modified Sugar Nucleotides To Probe the GDP-d-Mannose Dehydrogenase from Pseudomonas aeruginosa (2019)
Journal Article

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.

Gas-liquid flow hydrogenation of nitroarenes: Efficient access to a pharmaceutically relevant pyrrolobenzo[1,4]diazepine scaffold (2018)
Journal Article

Using a Tube-in-Tube device based on the amorphous Teflon AF-2400 fluoropolymer, a series of nitroarenes was hydrogenated to afford the corresponding aniline compounds. The system was then applied to the construction of a pyrrolobenzo[1,4]diazapene s... Read More about Gas-liquid flow hydrogenation of nitroarenes: Efficient access to a pharmaceutically relevant pyrrolobenzo[1,4]diazepine scaffold.

Recent advances in the enzymatic synthesis of sugar-nucleotides using nucleotidylyltransferases and glycosyltransferases (2018)
Journal Article

Sugar-nucleotides are imperative to carbohydrate metabolism and glycoconjugate biosynthesis. Enzymatic methods to access these key materials offer a powerful alternative to traditional chemical synthesis routes. Herein we review recent advances in th... Read More about Recent advances in the enzymatic synthesis of sugar-nucleotides using nucleotidylyltransferases and glycosyltransferases.

Chapter 18: Synthesis of 1,3,4,6-Tetra-O-acetyl-2-azido-2-deoxy-α,β-d- glucopyranose Using the Diazo-Transfer Reagent Imidazole-1- sulfonyl Azide Hydrogen Sulfate By Garrett T. Potter, Gordon C. Jayson, John M. Gardiner, Lorenzo Guazelli, and Gavin J. Miller (2018)
Journal Article

D-Glucosamine, and derivatives thereof, are found in many biologically important saccharides, including glycosaminoglycans (GAGs), and in various classes of oligosaccharides. Glucosamines can also serve as useful chirons. Consequently, synthetic deri... Read More about Chapter 18: Synthesis of 1,3,4,6-Tetra-O-acetyl-2-azido-2-deoxy-α,β-d- glucopyranose Using the Diazo-Transfer Reagent Imidazole-1- sulfonyl Azide Hydrogen Sulfate By Garrett T. Potter, Gordon C. Jayson, John M. Gardiner, Lorenzo Guazelli, and Gavin J. Miller.

Synthetic Site-Selectively Mono-6-O-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties In Vitro and Sensitizes Tumors to Cisplatin In Vivo (2016)
Journal Article

Heparan sulphate (HS), a ubiquitously expressed glycosaminoglycan (GAG), regulates multiple cellular functions by mediating interactions between numerous growth factors and their cell surface cognate receptors. However, the structural specificity of... Read More about Synthetic Site-Selectively Mono-6-O-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties In Vitro and Sensitizes Tumors to Cisplatin In Vivo.

Synthetic Site-Selectively Mono-6-<i>O</i>-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties <i>In Vitro</i> and Sensitizes Tumors to Cisplatin <i>In Vivo</i> (2016)
Journal Article

Heparan sulphate (HS), a ubiquitously expressed glycosaminoglycan (GAG), regulates multiple cellular functions by mediating interactions between numerous growth factors and their cell surface cognate receptors. However, the structural specificity of... Read More about Synthetic Site-Selectively Mono-6-<i>O</i>-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties <i>In Vitro</i> and Sensitizes Tumors to Cisplatin <i>In Vivo</i>.

Making the longest sugars: a chemical synthesis of heparin-related [4](n) oligosaccharides from 16-mer to 40-mer (2015)
Journal Article

The chemical synthesis of long oligosaccharides remains a major challenge. In particular, the synthesis of glycosaminoglycan (GAG) oligosaccharides belonging to the heparin and heparan sulfate (H/HS) family has been a high profile target, particularl... Read More about Making the longest sugars: a chemical synthesis of heparin-related [4](n) oligosaccharides from 16-mer to 40-mer.

Synthetic heparan sulfate dodecasaccharides reveal single sulfation site interconverts CXCL8 and CXCL12 chemokine biology (2015)
Journal Article

he multigram-scale synthesis of a sulfation-site programmed heparin-like dodecasaccharide is described. Evaluation alongside dodecasaccharides lacking this single glucosamine O6-sulfation, or having per-O6-sulfation, shows that site-specific modifica... Read More about Synthetic heparan sulfate dodecasaccharides reveal single sulfation site interconverts CXCL8 and CXCL12 chemokine biology.

Modular Synthesis of Heparin-Related Tetra-, Hexa- and Octasaccharides with Differential O-6 Protections: Programming for Regiodefined 6-O-Modifications (2015)
Journal Article

Heparin and heparan sulphate (H/HS) are important members of the glycosaminoglycan family of sugars that regulate a substantial number of biological processes. Such biological promiscuity is underpinned by hetereogeneity in their molecular structure.... Read More about Modular Synthesis of Heparin-Related Tetra-, Hexa- and Octasaccharides with Differential O-6 Protections: Programming for Regiodefined 6-O-Modifications.

Synthesis of L-Iduronic Acid Derivatives via [3.2.1] and [2.2.2] L-Iduronic Lactones from Bulk Glucose-Derived Cyanohydrin Hydrolysis: A Reversible Conformationally Switched Superdisarmed/Rearmed Lactone Route to Heparin Disaccharides (2015)
Journal Article

l-Idofuranoside cyanohydrin 1 is converted on large scale into a mixture of l-IdoA methyl pyranosides and furanosides, which is converged to provide short 2-step routes to bicyclic [3.2.1] or [2.2.2] l-iduronate lactones. The former is obtained via a... Read More about Synthesis of L-Iduronic Acid Derivatives via [3.2.1] and [2.2.2] L-Iduronic Lactones from Bulk Glucose-Derived Cyanohydrin Hydrolysis: A Reversible Conformationally Switched Superdisarmed/Rearmed Lactone Route to Heparin Disaccharides.

Synthesis of a heparin-related GlcN-IdoA sulfation-site variable disaccharide library and analysis by Raman and ROA spectroscopy (2014)
Journal Article

Synthesis of an array of differentially sulfated GlcN–IdoA disaccharides, accessible on good scale, directly from l-iduronate components is described. These are specifically directed to provide the sulfation variability at the key most common biologi... Read More about Synthesis of a heparin-related GlcN-IdoA sulfation-site variable disaccharide library and analysis by Raman and ROA spectroscopy.

Tetrasaccharide iteration synthesis of a heparin-like dodecasaccharide and radiolabelling for in vivo tissue distribution studies (2013)
Journal Article

Heparin-like oligosaccharides mediate numerous important biological interactions, of which many are implicated in various diseases. Synthetic improvements are central to the development of such oligosaccharides as therapeutics and, in addition, there... Read More about Tetrasaccharide iteration synthesis of a heparin-like dodecasaccharide and radiolabelling for in vivo tissue distribution studies.

Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2-and VEGF(165)-mediated endothelial cell functions (2013)
Journal Article

A concise chemical synthesis of a series of structurally-defined heparin-like oligosaccharides is described. This work provides an efficient entry to octa-, deca-, and dodecasaccharides, including the first synthesis of (GlcNS6S-IdoA2S)5 and (GlcNS6S... Read More about Efficient chemical synthesis of heparin-like octa-, deca- and dodecasaccharides and inhibition of FGF2-and VEGF(165)-mediated endothelial cell functions.

Thieme Chemistry Journal Awardees - Where are They Now? Synthesis of the Marine Glycolipid Dioctadecanoyl Discoside (2009)
Journal Article

The first synthesis of the inositol-containing marine glycolipid dioctadecanoyl discoside is reported. The key glycosylation reaction proceeds with ß-selectivity at reduced temperature. The separable anomers could be readily progressed to afford disc... Read More about Thieme Chemistry Journal Awardees - Where are They Now? Synthesis of the Marine Glycolipid Dioctadecanoyl Discoside.

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.