Synthesis and glycosidation of building blocks of D-altrosamine.

Presented herein is a streamlined synthesis of building blocks of a rare sugar D-altrosamine. Also investigated was the glycosylation of different glycosyl acceptors with differentially protected altrosamine donors. High facial stereoselectivity was achieved with 3-O-picoloyl donors and reactive glycosyl acceptors via the H-bond-mediated aglycone delivery (HAD) pathway. In contrast, glycosidations of the altrosamine donor equipped with the 3-O-benzoyl group were poorly stereoselective.

Do non-pharmacological sleep interventions affect anxiety symptoms? A meta-analysis.

Research indicates a bidirectional relationship between sleep and anxiety, with findings suggesting anxiety can precede poor sleep and vice versa. Evidence suggests sleep-related thought processes associated with anxiety are involved in the maintenance of insomnia. Previous meta-analyses provide some evidence to suggest cognitive behavioural therapy for insomnia moderately improves anxiety, yet little research has investigated the effect of other sleep interventions on anxiety symptoms. The aim of this meta-analysis was to review whether non-pharmacological sleep interventions have an impact on anxiety symptoms immediately post-intervention. A systematic search of electronic databases was conducted to identify all randomized control trials (RCTs) investigating non-pharmacological sleep interventions that included anxiety symptoms as an outcome. Forty-three RCTs (n = 5945) met full inclusion criteria and were included in a random-effects meta-analysis model. The combined effect size of non-pharmacological sleep interventions on anxiety symptoms was moderate (Hedges' g = -0.38), indicating a reduction in symptoms. Subgroup analyses found a moderate effect for those with additional physical health difficulties (g = -0.46), a moderate effect for those with additional mental health difficulties (g = -0.47) and a moderate effect for those with elevated levels of anxiety at baseline (g = -0.43). A secondary meta-analysis found a large effect of non-pharmacological sleep interventions on sleep-related thought processes (g = -0.92). These findings indicate non-pharmacological sleep interventions are effective in reducing anxiety and sleep-related thought processes, and these effects may be larger in patients with anxiety. This has clinical implications for considering sleep interventions in the treatment of anxiety.

Direct Synthesis of Glycans Containing Challenging ManNAcA Residues.

A method for direct, highly stereoselective synthesis of glycans containing ß-linked d-mannosaminuronic acid (ManNAcA) residues is reported herein, among which is the capsular polysaccharide of Staphylococcus aureus type 8. Previous chemical syntheses of this glycan relied on indirect methods comprising glucosylation followed by a multistep epimerization and oxidation sequence. The high ß-stereocontrol with direct glycosidation of 3-O-picoloylated ManNAcA donors was achieved using the H-bond-mediated aglycone delivery (HAD) reaction. A method to achieve complete α-ManNAcA stereoselectivity with 3-O-benzoylated donors is also reported.

Recent Advances in Stereocontrolled Mannosylation: Focus on Glycans Comprising Acidic and/or Amino Sugars.

The main focus of this review is to describe accomplishments made in the stereoselective synthesis of ß-linked mannosides functionalized with carboxyls or amines/amides. These ManNAc, ManA and ManNAcA residues found in many glycoconjugates, bacterial polysaccharides, and alginates have consistently captured interest of the glycoscience community both due to synthetic challenge and therapeutic potential.

A versatile approach to the synthesis of glycans containing mannuronic acid residues.

Reported herein is a new method for a highly effective synthesis of ß-glycosides from mannuronic acid donors equipped with the 3-O-picoloyl group. The stereocontrol of glycosylations was achieved by means of the H-bond-mediated aglycone delivery (HAD). The method was utilized for the synthesis of a tetrasaccharide linked viaß-(1 → 3)-mannuronic linkages. We have also investigated 3,6-lactonized glycosyl donors that provided moderate to high ß-manno stereoselectivity in glycosylations. A method to achieve complete α-manno stereoselectivity with mannuronic acid donors equipped with 3-O-benzoyl group is also reported.

A versatile approach to the synthesis of mannosamine glycosides.

O-Picoloyl protecting groups at remote positions can affect the stereoselectivity of glycosylation by means of the H-bond-mediated aglycone delivery (HAD) pathway. A new practical method for the stereoselective synthesis of ß-glycosides of mannosamine is reported. The presence of the O-picoloyl group at the C-3 position of a mannosamine donor can provide high or complete stereocontrol. The method was also utilized for the synthesis of a biologically relevant trisaccharide related to the capsular polysaccharide of Streptococcus pneumoniae serotype 4. Also reported herein is a method to achieve complete α-manno stereoselectivity with mannosamine donors equipped with 3-O-benzoyl group.

Synthesis of 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-manno derivatives as versatile building blocks.

Reported herein is the synthesis of a number of building blocks of 2-amino-2-deoxy-d-mannose from common d-glucose precursors.

Microarray Analysis of Oligosaccharide-Mediated Multivalent Carbohydrate-Protein Interactions and Their Heterogeneity.

Carbohydrate-protein interactions (CPIs) are involved in a wide range of biological phenomena. Hence, the characterization and presentation of carbohydrate epitopes that closely mimic the natural environment is one of the long-term goals of glycosciences. Inspired by the multivalency, heterogeneity and nature of carbohydrate ligand-mediated interactions, we constructed a combinatorial library of mannose and galactose homo- and hetero-glycodendrons to study CPIs. Microarray analysis of these glycodendrons with a wide range of biologically important plant and animal lectins revealed that oligosaccharide structures and heterogeneity interact with each other to alter binding preferences.

Understanding carbohydrate-protein interactions using homologous supramolecular chiral Ru(ii)-glyconanoclusters.

Multivalent glycodendrimers make promising tools to tackle the basic and translational research in the field of carbohydrate-mediated interactions. Despite advances in glycodendrimers and glycopolymers, the multivalent probes available to date are still far from being ideal biological mimics. This work demonstrates the inherent chirality of glycodendrimers to be one of the promising factors to generate different spatial carbohydrate micro-environments to modulate specific carbohydrate-protein interactions. By exploiting the host-guest strategy, chiral Ru(ii) complexes (Δ and Λ) and mannose capped ß-cyclodextrin (ß-CD), we generated a library of homologous metallo-glycodendrimers (MGDs) with sizes of 50-70 nm. These nanoclusters can enantioselectively bind to specific C-type lectins and displayed selectivity in cellular uptake. We also discovered their potential clathrin-mediated endocytotic pathway in DC-SIGN and SIGNR3-transfected cell lines. Finally, in vivo biodistribution and sequestration of MGDs was determined to understand the role of chirality mediated spatial arrangement in carbohydrate-mediated interactions.

Supramolecular scaffolds on glass slides as sugar based rewritable sensors for bacteria.

We describe here the sugar functionalized ß-cyclodextrin-ferrocene glass slides as fully reversible bacterial biosensors under the influence of external adamantane carboxylic acid. The prototype d-mannose - E. coli ORN 178 and l-fucose - P. aeruginosa interactions serve as a model to illustrate the new approach.