Gavin Miller's Outputs (89)

Towards the synthesis of a 2-deoxy-2-fluoro-d-mannose building block and characterisation of an unusual 2-S-phenyl anomeric pyridinium triflate salt via 1 → 2 S-migration (2024)
Journal Article
Evans, S. T., Tizzard, G. J., Field, R. A., & Miller, G. J. (2024). Towards the synthesis of a 2-deoxy-2-fluoro-d-mannose building block and characterisation of an unusual 2-S-phenyl anomeric pyridinium triflate salt via 1 → 2 S-migration. Carbohydrate Research, 545, Article 109275. https://doi.org/10.1016/j.carres.2024.109275

Regio- and stereo-selective synthetic routes to 2-deoxy-2-fluoro-d-mannose building blocks are often experimentally challenging when using Selectfluor with the corresponding glycal. We targeted a late-stage method to introduce fluorine in a stereospe... Read More about Towards the synthesis of a 2-deoxy-2-fluoro-d-mannose building block and characterisation of an unusual 2-S-phenyl anomeric pyridinium triflate salt via 1 → 2 S-migration.

Synthesis of Nucleoside Analogs Containing Sulfur or Selenium Replacements of the Ribose Ring Oxygen or Carbon. (2024)
Journal Article
Benckendorff, C. M. M., Sunde-Brown, P., Ní Cheallaigh, A., & Miller, G. J. (2024). Synthesis of Nucleoside Analogs Containing Sulfur or Selenium Replacements of the Ribose Ring Oxygen or Carbon. Journal of Organic Chemistry, 89(23), 16977-16989. https://doi.org/10.1021/acs.joc.4c02409

Nucleoside analogs have proven highly successful in many pharmaceutical intervention strategies, and continued exploration of next generation structural motifs is required. Herein we discuss recent advances toward the chemical synthesis of heteroatom... Read More about Synthesis of Nucleoside Analogs Containing Sulfur or Selenium Replacements of the Ribose Ring Oxygen or Carbon..

Sugar-Coated: Can Multivalent Glycoconjugates Improve upon Nature’s Design? (2024)
Journal Article
Leslie, K. G., Berry, S. S., Miller, G. J., & Mahon, C. S. (2024). Sugar-Coated: Can Multivalent Glycoconjugates Improve upon Nature’s Design?. Journal of the American Chemical Society, 146(40), 27215-27232. https://doi.org/10.1021/jacs.4c08818

Multivalent interactions between receptors and glycans play an important role in many different biological processes, including pathogen infection, self-recognition, and the immune response. The growth in the number of tools and techniques toward the... Read More about Sugar-Coated: Can Multivalent Glycoconjugates Improve upon Nature’s Design?.

Benzoylation of Tetrols: A Comparison of Regioselectivity Patterns for O- and S-Glycosides of d-Galactose (2024)
Journal Article
Porter, J., Roberts, J., & Miller, G. J. (in press). Benzoylation of Tetrols: A Comparison of Regioselectivity Patterns for O- and S-Glycosides of d-Galactose. Journal of Organic Chemistry, https://doi.org/10.1021/acs.joc.4c01508

Efficient protecting group strategies are important for glycan synthesis and represent a unique synthetic challenge in differentiating sugar ring hydroxyl groups. Direct methods to enable regioselective protecting group installation are thus desirabl... Read More about Benzoylation of Tetrols: A Comparison of Regioselectivity Patterns for O- and S-Glycosides of d-Galactose.

Tandem One-Pot Biocatalytic Oxidation and Wittig Reaction in Water (2024)
Journal Article
Wahart, A. J. C., Beardmore, L. N. D., Field, R. A., Cosgrove, S. C., & Miller, G. J. (in press). Tandem One-Pot Biocatalytic Oxidation and Wittig Reaction in Water. Organic Letters, 26(31), 6642-6646. https://doi.org/10.1021/acs.orglett.4c02201

We explore biocatalytic aldehyde generation under aqueous conditions, concomitantly delivering access to a one-pot Wittig reaction using stabilized phosphoranes and granting diverse alkene products. Using a recombinant choline oxidase mutant, we firs... Read More about Tandem One-Pot Biocatalytic Oxidation and Wittig Reaction in Water.

Adaptable Synthesis of Chondroitin Sulfate Disaccharide Subtypes Preprogrammed for Regiospecific O‐Sulfation (2024)
Journal Article
Wootton, H. S., Berry, S. S., Ferguson, E. L., Mahon, C. S., & Miller, G. J. (in press). Adaptable Synthesis of Chondroitin Sulfate Disaccharide Subtypes Preprogrammed for Regiospecific O‐Sulfation. European Journal of Organic Chemistry, Article e202400587. https://doi.org/10.1002/ejoc.202400587

A divergent synthetic route to chondroitin sulfate (CS) disaccharide precursors, including rarer subtypes such as CS‐D, has been developed. From common intermediates, a series of thioglycoside D‐glucosyl donors and 4,6‐O‐benzylidene protected D‐galac... Read More about Adaptable Synthesis of Chondroitin Sulfate Disaccharide Subtypes Preprogrammed for Regiospecific O‐Sulfation.

Exploring a Gemcitabine-Glucose Hybrid as a Glycoconjugate Prodrug (2024)
Journal Article
Porter, J., Noble, A. R., Signoret, N., Fascione, M. A., & Miller, G. J. (in press). Exploring a Gemcitabine-Glucose Hybrid as a Glycoconjugate Prodrug. ACS Omega, 9(29), 31703-31713. https://doi.org/10.1021/acsomega.4c02417

Nucleoside analogues are established treatments for cancer and viral infection. Gemcitabine is a commonly employed nucleoside analogue displaying anticancer properties against a range of tumor types but is rapidly inactivated in vivo. Efforts to bols... Read More about Exploring a Gemcitabine-Glucose Hybrid as a Glycoconjugate Prodrug.

Methyl and Benzyl (Ethyl 3,4-di-O-benzyl-2-O-benzoyl-1-thio-β-d-glucopyranosyl)uronate (2024)
Journal Article
Wootton, H. S., & J. Miller, G. (2024). Methyl and Benzyl (Ethyl 3,4-di-O-benzyl-2-O-benzoyl-1-thio-β-d-glucopyranosyl)uronate. Molbank, 2024(3), Article M1847. https://doi.org/10.3390/M1847

Methyl and benzyl (ethyl 3,4-di-O-benzyl-2-O-benzoyl-1-thio-β-D-glucopyranosyl)uronate were synthesised from a protected thioglycoside in three steps. A regioselective ring opening of the benzylidene acetal with BH3.THF generated C6-OH material, whic... Read More about Methyl and Benzyl (Ethyl 3,4-di-O-benzyl-2-O-benzoyl-1-thio-β-d-glucopyranosyl)uronate.

Correction: Virtual screening, identification and in vitro validation of small molecule GDP-mannose dehydrogenase inhibitors (2024)
Journal Article
Dolan, J. P., Ahmadipour, S., Wahart, A. J. C., Cheallaigh, A. N., Sari, S., Eurtivong, C., …Miller, G. J. (in press). Correction: Virtual screening, identification and in vitro validation of small molecule GDP-mannose dehydrogenase inhibitors. RSC Chemical Biology, https://doi.org/10.1039/d4cb90026j

Correction for ‘Virtual screening, identification and in vitro validation of small molecule GDP-mannose dehydrogenase inhibitors’ by Jonathan P. Dolan et al., RSC Chem. Biol., 2023, 4, 865–870, https://doi.org/10.1039/D3CB00126A.

Biocatalytic Nucleobase Diversification of 4'‐Thionucleosides and Application of Derived 5‐Ethynyl‐4'‐thiouridine for RNA synthesis detection (2024)
Journal Article
Westarp, S., Benckendorff, C., Motter, J., Rohrs, V., Sanghvi, Y., Neubauer, P., …Miller, G. J. (in press). Biocatalytic Nucleobase Diversification of 4'‐Thionucleosides and Application of Derived 5‐Ethynyl‐4'‐thiouridine for RNA synthesis detection. Angewandte Chemie, Article e202405040. https://doi.org/10.1002/ange.202405040

Nucleoside and nucleotide analogues have proven to be transformative in the treatment of viral infections and cancer. One branch of structural modification to deliver new nucleoside analogue classes explores replacement of canonical ribose oxygen wit... Read More about Biocatalytic Nucleobase Diversification of 4'‐Thionucleosides and Application of Derived 5‐Ethynyl‐4'‐thiouridine for RNA synthesis detection.

Biocatalytic Nucleobase Diversification of 4'-Thionucleosides and Application of Derived 5-Ethynyl-4'-thiouridine for RNA synthesis detection. (2024)
Journal Article
Westarp, S., Benckendorff, C., Motter, J., Rohrs, V., Sanghvi, Y., Neubauer, P., …Miller, G. J. (in press). Biocatalytic Nucleobase Diversification of 4'-Thionucleosides and Application of Derived 5-Ethynyl-4'-thiouridine for RNA synthesis detection. Angewandte Chemie, Article e202405040. https://doi.org/10.1002/anie.202405040

Nucleoside and nucleotide analogues have proven to be transformative in the treatment of viral infections and cancer. One branch of structural modification to deliver new nucleoside analogue classes explores replacement of canonical ribose oxygen wit... Read More about Biocatalytic Nucleobase Diversification of 4'-Thionucleosides and Application of Derived 5-Ethynyl-4'-thiouridine for RNA synthesis detection..

3’-O-β-Glycosylation of nucleoside analogues using a promiscuous bacterial glycosyltransferase (2024)
Working Paper
Dolan, J., Keenan, T., Benckendorff, C., Ní Cheallaigh, A., Fascione, M., & Miller, G. 3’-O-β-Glycosylation of nucleoside analogues using a promiscuous bacterial glycosyltransferase

Synthesis of a heparan sulfate tetrasaccharide using automated glycan assembly † (2024)
Journal Article
Pongener, I., Sletten, E. T., Danglad-Flores, J., Seeberger, P. H., & Miller, G. J. (in press). Synthesis of a heparan sulfate tetrasaccharide using automated glycan assembly †. Organic and Biomolecular Chemistry, https://doi.org/10.1039/d3ob01909h

Herein we utilise automated glycan assembly to complete solid-phase synthesis of defined heparan sulfate oligosaccharides, employing challenging d-glucuronate disaccharide donors. Using an orthogonally protected d-GlcN-α-d-GlcA donor, milligram-scale... Read More about Synthesis of a heparan sulfate tetrasaccharide using automated glycan assembly †.

Purine nucleoside antibiotics: recent synthetic advances harnessing chemistry and biology (2024)
Journal Article
Motter, J., Benckendorff, C. M. M., Westarp, S., Sunde-Brown, P., Neubauer, P., Kurreck, A., & Miller, G. J. (in press). Purine nucleoside antibiotics: recent synthetic advances harnessing chemistry and biology. Natural Product Reports, https://doi.org/10.1039/d3np00051f

Covering: 2019 to 2023 Nucleoside analogues represent one of the most important classes of small molecule pharmaceuticals and their therapeutic development is successfully established within oncology and for the treatment of viral infections. However... Read More about Purine nucleoside antibiotics: recent synthetic advances harnessing chemistry and biology.

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.

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
Hoolachan, J. M., McCallion, E., Sutton, E. R., Çetin, Ö., Pacheco-Torres, P., Dimitriadi, M., …Bowerman, M. (2024). A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models. Human molecular genetics, 33(5), 400–425. https://doi.org/10.1093/hmg/ddad192

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..

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..

Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manβ1,4GlcNAc library † (2023)
Journal Article
Keenan, T., Hatton, N. E., Porter, J., Vendeville, J., Wheatley, D. E., Ghirardello, M., …Fascione, M. A. (in press). Reverse thiophosphorylase activity of a glycoside phosphorylase in the synthesis of an unnatural Manβ1,4GlcNAc library †. Chemical Science, 14(42), 11638-11646. https://doi.org/10.1039/d3sc04169g

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 †.

Preparation of a 4′‐Thiouridine Building‐Block for Solid‐Phase Oligonucleotide Synthesis (2023)
Journal Article
Benckendorff, C. M. M., Sanghvi, Y. S., & Miller, G. J. (2023). Preparation of a 4′‐Thiouridine Building‐Block for Solid‐Phase Oligonucleotide Synthesis. Current Protocols in Neuroscience, 3(9), Article e878. https://doi.org/10.1002/cpz1.878

Starting from a commercially available thioether, we report a nine‐step synthesis of a 4′‐thiouridine phosphoramidite building‐block. We install the uracil nucleobase using Pummerer‐type glycosylation of a sulfoxide intermediate followed by a series... Read More about Preparation of a 4′‐Thiouridine Building‐Block for Solid‐Phase Oligonucleotide Synthesis.

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 †.