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 stereospecific manner using inversion via a triflate. Accordingly, synthesis of a conventionally protected 2-deoxy-2-fluoro-d-mannose β-thioglycoside donor, directly applicable to oligosaccharide synthesis, was attempted using C2-triflate inversion of the corresponding d-glucoside with TBAF.
View Article and Find Full Text PDFWe 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 first undertake biocatalytic alcohol oxidation across a range of functional aliphatic primary alcohols, demonstrating a remarkable substrate tolerance for this enzyme, including chloride, bromide, azide, -methyl, and alkynyl groups. Following this, we extend capability and deliver a practicable milligram-scale one-pot Wittig reaction in water.
View Article and Find Full Text PDFCotton ovule cultures are a promising platform for exploring biofabrication of fibers with tailored properties. When the ovules' growth medium is supplemented with chemically synthesized cellulose precursors, it results in their integration into the developing fibers, thereby tailoring their end properties. Here, we report the feeding of synthetic glucosyl phosphate derivative, 6-deoxy-6-fluoro-glucose-1-phosphate (6F-Glc-1P) to cotton ovules growing , demonstrating the metabolic incorporation of 6F-Glc into the fibers with enhanced mechanical properties and moisture-retention capacity while emphasizing the role of molecular hierarchical architecture in defining functional characteristics and mechanical properties.
View Article and Find Full Text PDFIn structural terms, the sialic acids are a large family of nine carbon sugars based around an alpha-keto acid core. They are widely spread in nature, where they are often found to be involved in molecular recognition processes, including in development, immunology, health and disease. The prominence of sialic acids in infection is a result of their exposure at the non-reducing terminus of glycans in diverse glycolipids and glycoproteins.
View Article and Find Full Text PDFQS-21 is a potent vaccine adjuvant currently sourced by extraction from the Chilean soapbark tree. It is a key component of human vaccines for shingles, malaria, coronavirus disease 2019 and others under development. The structure of QS-21 consists of a glycosylated triterpene scaffold coupled to a complex glycosylated 18-carbon acyl chain that is critical for immunostimulant activity.
View Article and Find Full Text PDFPhotodynamic therapy (PDT) uses a non-toxic light sensitive molecule, a photosensitiser, that releases cytotoxic reactive oxygen species upon activation with light of a specific wavelength. Here, glycan-modified 16 nm gold nanoparticles (glycoAuNPs) were explored for their use in targeted PDT, where the photosensitiser was localised to the target cell through selective glycan-lectin interactions. Polyacrylamide (PAA)-glycans were chosen to assess glycan binding to the cell lines.
View Article and Find Full Text PDFUpon undergoing mucoid conversion within the lungs of cystic fibrosis patients, the pathogenic bacterium synthesises copious quantities of the virulence factor and exopolysaccharide alginate. The enzyme guanosine diphosphate mannose dehydrogenase (GMD) catalyses the rate-limiting step and irreversible formation of the alginate sugar nucleotide building block, guanosine diphosphate mannuronic acid. Since there is no corresponding enzyme in humans, strategies that could prevent its mechanism of action could open a pathway for new and selective inhibitors to disrupt bacterial alginate production.
View Article and Find Full Text PDFInterpreting diffuse intensities in electron diffraction patterns can be challenging in samples with high atomic-level complexity, as often is the case with multi-principal element alloys. For example, diffuse intensities in electron diffraction patterns from simple face-centred cubic (fcc) and related alloys have been attributed to short-range order, medium-range order or a variety of different {111} planar defects, including thin twins, thin hexagonal close-packed layers, relrod spiking and incomplete ABC stacking. Here we demonstrate that many of these diffuse intensities, including [Formula: see text]{422} and [Formula: see text]{311} in ⟨111⟩ and ⟨112⟩ selected area diffraction patterns, respectively, are due to reflections from higher-order Laue zones.
View Article and Find Full Text PDFA few α-glucan debranching enzymes (DBEs) of the large glycoside hydrolase family 13 (GH13), also known as the α-amylase family, have been shown to catalyze transglycosylation as well as hydrolysis. However, little is known about their acceptor and donor preferences. Here, a DBE from barley, limit dextrinase (LD), is used as a case study.
View Article and Find Full Text PDFThe β-glucans are structurally varied, naturally occurring components of the cell walls, and storage materials of a variety of plant and microbial species. In the human diet, mixed-linkage glucans [MLG - β-(1,3/4)-glucans] influence the gut microbiome and the host immune system. Although consumed daily, the molecular mechanism by which human gut Gram-positive bacteria utilize MLG largely remains unknown.
View Article and Find Full Text PDFβ-(1,2)-Mannan antigens incorporated into vaccines candidates for immunization studies, showed that antibodies raised against β-(1,2)-mannotriose antigens can protect against disseminated candidiasis. Until recently, β-(1,2)- mannans could only be obtained by isolation from microbial cultures, or by lengthy synthetic strategies involving protecting group manipulation. The discovery of two β-(1,2)-mannoside phosphorylases, Teth514_1788 and Teth514_1789, allowed efficient access to these compounds.
View Article and Find Full Text PDFFor several years, experts have warned about the lack of diversity in genetic research databases, and researchers have devoted time and resources to recruiting subjects from underrepresented subgroups. In this study, we review published reports in academic journals of genetic studies of Alzheimer's disease to note whether demographic diversity was indicated in the reports and, if so, the extent of representation of non-European subjects over the period from 1997 to 2022. We use multivariate regression analysis to analyze changes over time and to explain variation across studies.
View Article and Find Full Text PDFWe utilize rotationally resolved Chirped-Pulse Fourier Transform millimeter-wave spectroscopy to study photodissociation dynamics of 1,3,5-Triazine (-Triazine) to form 3 HCN molecules. The (VPD) of the photofragments contains mechanistic details of the reaction. This photodissociation is performed using 266 nm radiation transverse to a seeded supersonic jet.
View Article and Find Full Text PDFThrough qualitative surveys, a team of law students, law professors, physicians, and residents explored the perceptions of neurology residents towards referral to appropriate legal resources in an academic training program. Respondents reported feeling uncomfortable screening their patients for health-harming legal needs, which many attributed to a lack of training in this area. These findings indicate that neurology residents would benefit from training on screening for social factors that may be impacting their patients' health.
View Article and Find Full Text PDFEuglenoids (Euglenida) are unicellular flagellates possessing exceptionally wide geographical and ecological distribution. Euglenoids combine a biotechnological potential with a unique position in the eukaryotic tree of life. In large part these microbes owe this success to diverse genetics including secondary endosymbiosis and likely additional sources of genes.
View Article and Find Full Text PDFSufferers of cystic fibrosis are at significant risk of contracting chronic bacterial lung infections. The dominant pathogen in these cases is mucoid Such infections are characterised by overproduction of the exopolysaccharide alginate. We present herein the design and chemoenzymatic synthesis of sugar nucleotide tools to probe a critical enzyme within alginate biosynthesis, GDP-mannose dehydrogenase (GMD).
View Article and Find Full Text PDFThe chemoenzymatic synthesis of a series of dual N- and C-terminal-functionalized cholera toxin B subunit (CTB) glycoconjugates is described. Mucin 1 peptides bearing different levels of Tn antigen glycosylation [MUC1(Tn)] were prepared solid-phase peptide synthesis. Using sortase-mediated ligation, the MUC1(Tn) epitopes were conjugated to the C-terminus of CTB in a well-defined manner allowing for high-density display of the MUC1(Tn) epitopes.
View Article and Find Full Text PDFCurrent point-of-care lateral flow immunoassays, such as the home pregnancy test, rely on proteins as detection units ( antibodies) to sense for analytes. Glycans play a fundamental role in biological signalling and recognition events such as pathogen adhesion and hence they are promising future alternatives to antibody-based biosensing and diagnostics. Here we introduce the potential of glycans coupled to gold nanoparticles as recognition agents for lateral flow diagnostics.
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
October 2022
Ro-vibronic spectra of the CO carbon monoxide isotopologue were obtained with (i) emission spectroscopy in the visible region using a Bruker IFS 125HR spectrometer (University of Rzeszów) and (ii) vacuum-ultraviolet absorption spectroscopy using the wave-front-division spectrometer on the DESIRS beamline of the SOLEIL synchrotron. A deperturbation analysis of the CO AΠ(v = 1) level was conducted from 598 observed transitions from the BΣ - AΠ(0, 1), CΣ - AΠ(0, 1), AΠ - XΣ(1, 0), BΣ - XΣ(0, 0), CΣ - XΣ(0, 0), IΣ - XΣ(2, 0) bands and five further nominally forbidden bands. An effective Hamiltonian and term-value fitting analysis was implemented.
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