Alginates –A Seaweed product: Its Properties and Applications

Alginates are natural polysaccharides available as seaweed products. They possess several properties due to their molecular structure made of bipolymeric α-L-Guluronic acid and β-D-Mannuronic acid polymers. Alginates have several properties such as film-forming ability, pH responsiveness, and gelling, hydrophilicity, biocompatibility, biodegradability, non-toxic, processability and ionic crosslinking. They’re commonly used in several industries, including food, pharmaceuticals, dental applications, welding rods and scaffolding. Due to their gelling and non-toxic properties, as well as their abundance in nature, the cosmetics and healthcare industries have shown a great deal of interest in biodegradable polymers in general and alginates particularly over the last few decades.

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

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 carboxylates would underpin provision of new oligo-/polysaccharide materials with alternate physicochemical properties. Presented herein is our synthesis of mannuronic acid building blocks, appropriately modified at the carboxylate C6 position with a bioisosteric tetrazole. Thioglycosides containing a protected C6-tetrazole are accessed from a C6-nitrile, through dipolar cycloaddition using NaN3 with n-Bu2SnO. We also demonstrate access to orthogonally C4-protected donors, suitable for iterative oligosaccharide synthesis. The development of these building blocks is showcased to access anomeric 3-aminopropyl- and 1-phosphate free sugars containing this non-native motif.

Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms

Here, we report the first complete genomes of three cultivable treponeme species from bovine digital dermatitis (DD) skin lesions, two comparative human treponemes, considered indistinguishable from bovine DD species, and a bovine gastrointestinal (GI) treponeme isolate. Key genomic differences between bovine and human treponemes implicate microbial mechanisms that enhance knowledge of how DD, a severe disease of ruminants, has emerged into a prolific, worldwide disease. Bovine DD treponemes have additional oxidative stress genes compared to nearest human-isolated relatives, suggesting better oxidative stress tolerance, and potentially explaining how bovine strains can colonize skin surfaces. Comparison of both bovine DD and GI treponemes as well as bovine pathogenic and human non-pathogenic saprophyte Treponema phagedenis strains indicates genes encoding a five-enzyme biosynthetic pathway for production of 2,3-diacetamido-2,3-dideoxy-d-mannuronic acid, a rare di-N-acetylated mannuronic acid sugar, as important for pathogenesis. Bovine T. phagedenis strains further differed from human strains by having unique genetic clusters including components of a type IV secretion system and a phosphate utilisation system including phoU, a gene associated with osmotic stress survival. Proteomic analyses confirmed bovine derived T. phagedenis exhibits expression of PhoU but not the putative secretion system, whilst the novel mannuronic acid pathway was expressed in near entirety across the DD treponemes. Analysis of osmotic stress response in water identified a difference between bovine and human T. phagedenis with bovine strains exhibiting enhanced survival. This novel mechanism could enable a selective advantage, allowing environmental persistence and transmission of bovine T. phagedenis. Finally, we investigated putative outer membrane protein (OMP) ortholog families across the DD treponemes and identified several families as multi-specific adhesins capable of binding extra cellular matrix (ECM) components. One bovine pathogen specific adhesin ortholog family showed considerable serodiagnostic potential with the Treponema medium representative demonstrating considerable disease specificity (91.6%). This work has shed light on treponeme host adaptation and has identified candidate molecules for future diagnostics, vaccination and therapeutic intervention.

Chemical synthesis of C6-tetrazole D-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

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 polysaccharide backbone. An ability to design and synthesise isosteres of these carboxylates would ultimately enable access to new alginate systems possessing different physicochemical properties. We present herein an approach to the chemical synthesis of alginate building blocks, modified at the carboxylate C6 position with bioisosteric tetrazole. The development of this synthesis enables utilisation of C6-tetrazole donors to deliver anomeric phosphate and 3-aminopropyl free sugars containing this motif. Access to these building blocks will further enable glycosylation methodologies to be explored that incorporate tetrazole as a bioisostere within uronic acid-containing carbohydrates.