Polyvalent Mannuronic Acid-Coated Gold Nanoparticles for Probing Multivalent Lectin-Glycan Interaction and Blocking Virus Infection.

Multivalent lectin-glycan interactions (MLGIs) are vital for viral infection, cell-cell communication and regulation of immune responses. Their structural and biophysical data are thus important, not only for providing insights into their underlying mechanisms but also for designing potent glycoconjugate therapeutics against target MLGIs. However, such information remains to be limited for some important MLGIs, significantly restricting the research progress.

Polyvalent Glycomimetic-Gold Nanoparticles Revealing Critical Roles of Glycan Display on Multivalent Lectin-Glycan Interaction Biophysics and Antiviral Properties.

Multivalent lectin-glycan interactions (MLGIs) are widespread and vital for biology, making them attractive therapeutic targets. Unfortunately, the structural and biophysical mechanisms of several key MLGIs remain poorly understood, limiting our ability to design spatially matched glycoconjugates as potential therapeutics against specific MLGIs. We have recently demonstrated that natural oligomannose-coated nanoparticles are powerful probes for MLGIs.

Probing the pH-dependency of DC-SIGN/R multivalent lectin-glycan interactions using polyvalent glycan-gold nanoparticles.

The dendritic cell tetrameric lectin, DC-SIGN, and its closely related endothelial cell lectin, DC-SIGNR (collectively abbreviated as DC-SIGN/R) play a key role in the binding and transmission of deadly viruses, including Ebola, HIV, HCV, and SARS-CoV-2. Their virus binding/release processes involve a gradually acidifying environment following the natural intracellular trafficking pathways. Therefore, understanding DC-SIGN/R's pH-dependent binding properties with glycan ligands is of great importance.

The Retaining Pse5Ac7Ac Pseudaminyltransferase KpsS1 Defines a Previously Unreported glycosyltransferase family (GT118).

Cell surface sugar 5,7-diacetyl pseudaminic acid (Pse5Ac7Ac) is a bacterial analogue of the ubiquitous sialic acid, Neu5Ac, and contributes to the virulence of a number of multidrug resistant bacteria, including ESKAPE pathogens Pseudomonas aeruginosa, and Acinetobacter baumannii. Despite its discovery in the surface glycans of bacteria over thirty years ago, to date no glycosyltransferase enzymes (GTs) dedicated to the synthesis of a pseudaminic acid glycosidic linkage have been unequivocally characterised in vitro. Herein we demonstrate that A.

Polyvalent Nano-Lectin Potently Neutralizes SARS-CoV-2 by Targeting Glycans on the Viral Spike Protein.

Mutations in spike (S) protein epitopes allow SARS-CoV-2 variants to evade antibody responses induced by infection and/or vaccination. In contrast, mutations in glycosylation sites across SARS-CoV-2 variants are very rare, making glycans a potential robust target for developing antivirals. However, this target has not been adequately exploited for SARS-CoV-2, mostly due to intrinsically weak monovalent protein-glycan interactions.

Polyvalent Glycan Functionalized Quantum Nanorods as Mechanistic Probes for Shape-Selective Multivalent Lectin-Glycan Recognition.

Multivalent lectin-glycan interactions (MLGIs) are widespread in biology and hold the key to many therapeutic applications. However, the underlying structural and biophysical mechanisms for many MLGIs remain poorly understood, limiting our ability to design glycoconjugates to potently target specific MLGIs for therapeutic intervention. Glycosylated nanoparticles have emerged as a powerful biophysical probe for MLGIs, although how nanoparticle shape affects the MLGI molecular mechanisms remains largely unexplored.

Polyvalent Glycan Quantum Dots as a Multifunctional Tool for Revealing Thermodynamic, Kinetic, and Structural Details of Multivalent Lectin-Glycan Interactions.

Multivalent lectin-glycan interactions (MLGIs) are widespread and vital for biology. Their binding biophysical and structural details are thus highly valuable, not only for the understanding of binding affinity and specificity mechanisms but also for guiding the design of multivalent therapeutics against specific MLGIs. However, effective techniques that can reveal all such details remain unavailable.

Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands.

Galectins are potential biomarkers and therapeutic targets. However, galectins display broad affinity towards β-galactosides meaning glycan-based (nano)biosensors lack the required selectivity and affinity. Using a polymer-stabilized nanoparticle biosensing platform, we herein demonstrate that the specificity of immobilised lacto--biose towards galectins can be 'turned on/off' by using site-specific glycan fluorination and in some cases reversal of specificity can be achieved.

Glycan-Gold Nanoparticles as Multifunctional Probes for Multivalent Lectin-Carbohydrate Binding: Implications for Blocking Virus Infection and Nanoparticle Assembly.

Multivalent lectin-glycan interactions are widespread in biology and are often exploited by pathogens to bind and infect host cells. Glycoconjugates can block such interactions and thereby prevent infection. The inhibition potency strongly depends on matching the spatial arrangement between the multivalent binding partners.

The characterisation of a galactokinase from Streptomyces coelicolor.

Promiscuous galactokinases (GalKs), which catalyse the ATP dependent phosphorylation of galactose in nature, have been widely exploited in biotechnology for the rapid synthesis of diverse sugar-1-phosphates. This work focuses on the characterisation of a bacterial GalK from Streptomyces coelicolor (ScGalK), which was overproduced in Escherichia coli and shown to phosphorylate galactose. ScGalK displayed a broad substrate tolerance, with activity towards Gal, GalN, Gal3D, GalNAc, Man and L-Ara.

Using automated glycan assembly (AGA) for the practical synthesis of heparan sulfate oligosaccharide precursors.

Herein we report synthesis of complex heparan sulfate oligosaccharide precursors by automated glycan assembly using disaccharide donor building blocks. Rapid access to a hexasaccharide was achieved through iterative solid phase glycosylations on a photolabile resin using Glyconeer™, an automated oligosaccharide synthesiser, followed by photochemical cleavage and glycan purification using simple flash column chromatography.

Site-selective C-C modification of proteins at neutral pH using organocatalyst-mediated cross aldol ligations.

The bioconjugation of proteins with small molecules has proved an invaluable strategy for probing and perturbing biological mechanisms. The general use of chemical methods for protein functionalisation can be limited however by the requirement for complicated reaction partners to be present in large excess, and harsh conditions which are incompatible with many protein scaffolds. Herein we describe a site-selective organocatalyst-mediated protein aldol ligation (OPAL) that affords stable carbon-carbon linked bioconjugates at neutral pH.

Development of a cell permeable red-shifted CHEF-based chemosensor for Al(3+) ion by controlling PET.

A structurally modified quinazoline derivative (L) acts as highly selective chemosensor for Al(3+) ions in DMSO-H2O (1:9, v/v) over the other competitive metal ions. L shows a red shifted fluorescence after the addition of Al(3+) ions and later the further fluorescence enhancement is due to chelation enhanced fluorescence (CHEF) through inhibition of photoinduced electron transfer (PET). This probe (L) detects Al(3+) ions as low as 9nM in DMSO-H2O (1:9, v/v) at biological pH.

Chemical synthesis of a tetrasaccharide related to the exocellular polysaccharide from Rhodococcus sp. RHA1.

Chemical synthesis of the tetrasaccharide related to the exocellular polysaccharide from Rhodococcus sp. RHA1 is reported. The stereoselective glycosylations were achieved by activation of the thioglycoside donors using N-iodosuccinimide in the presence of La(OTf)3 varying temperature per the need of 1,2-cis or 1,2-trans glycosylations.

Synthesis of two trisaccharides related to the hepatoprotective phenylethanoids leonoside E and F isolated from Leonurus japonicus Houtt.

The chemical synthesis of two trisaccharides related to leonoside E and F is reported. The target oligosaccharides were prepared in the form of their p-methoxyphenyl glycosides using a common disaccharide acceptor. All reaction steps were high yielding (>80%) and the stereoselective glycosylations were achieved by activation of the thioglycoside donors using N-iodosuccinimide in the presence of La(OTf)3.