Advances in carbohydrate chemistry have certainly made common oligosaccharides much more accessible. However, many current methods still rely heavily upon specialized knowledge of carbohydrate chemistry. The application of automated technologies to chemical and life science applications such as genomics and proteomics represents a vibrant field. These automated technologies also present opportunities for their application to organic synthesis, including that of the synthesis of oligosaccharides. However, application of automated methods to the synthesis of carbohydrates is an underdeveloped area as compared to other classes of biomolecules. The overarching goal of this review article is to present the advances that have been made at the interface of carbohydrate chemistry and automated technology.

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Automated Chemical Oligosaccharide Synthesis: Novel Approach to Traditional Challenges.

Carbohydrates, which are ubiquitously distributed throughout the three domains of life, play significant roles in a variety of vital biological processes. Access to unique and homogeneous carbohydrate materials is important to understand their physical properties, biological functions, and disease-related features. It is difficult to isolate carbohydrates in acceptable purity and amounts from natural sources. Therefore, complex saccharides with well-defined structures are often most conviently accessed through chemical syntheses. Two major hurdles, regioselective protection and stereoselective glycosylation, are faced by carbohydrate chemists in synthesizing these highly complicated molecules. Over the past few years, there has been a radical change in tackling these problems and speeding up the synthesis of oligosaccharides. This is largely due to the development of one–pot protection, one–pot glycosylation, and one–pot protection–glycosylation protocols and streamlined approaches to orthogonally protect...

"One-Pot" Protection, Glycosylation, and Protection-Glycosylation Strategies of Carbohydrates.

The failure of mammalian CNS neurons to regenerate their axons derives from a combination of intrinsic deficits and extrinsic factors. Following injury, chondroitin sulfate proteoglycans (CSPGs) within the glial scar inhibit axonal regeneration, an action mediated by the sulfated glycosaminoglycan (GAG) chains of CSPGs, especially those with 4-sulfated (4S) sugars. Arylsulfatase B (ARSB) selectively cleaves 4S groups from the non-reducing ends of GAG chains without disrupting other, growth-permissive motifs. We demonstrate that ARSB is effective in reducing the inhibitory actions of CSPGs both in in vitro models of the glial scar and after optic nerve crush (ONC) in adult mice. ARSB is clinically approved for replacement therapy in patients with mucopolysaccharidosis VI and therefore represents an attractive candidate for translation to the human CNS.

/pdf/identification-of-a-critical-sulfation-in-chondroitin-that-4a5bw8c4xx.pdf

Identification of a critical sulfation in chondroitin that inhibits axonal regeneration

Review: Advances in preparation of chitooligosaccharides with heterogeneous sequences and their bioactivity.

Herein, we reported on a highly efficient glycosylation reaction comprising two chronological meticulously designed catalytic cycles: (1) rhodium-catalyzed formation of sulfonium ylide and (2) Bronsted acid-catalyzed formation of sulfonium ion. This protocol highlighted an effective and robust tactic to prepare a glycosyl sulfonium ion from a glycosyl sulfonium ylide precursor amenable for glycosylation.

Glycosylation Enabled by Successive Rhodium(II) and Brønsted Acid Catalysis.

The total synthesis of TMG-chitotriomycin using an automated electrochemical synthesizer for the assembly of carbohydrate building blocks is demonstrated We have successfully prepared a precursor of TMG-chitotriomycin, which is a structurally-pure tetrasaccharide with typical protecting groups, through the methodology of automated electrochemical solution-phase synthesis developed by us The synthesis of structurally well-defined TMG-chitotriomycin has been accomplished in 10-steps from a disaccharide building block

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-13-93.pdf

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block.

Synthesis of chondroitin sulfate CC and DD tetrasaccharides and interactions with 2H6 and LY111.

Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a factor involved in the suppression of myogenic differentiation. CS comprises two repeating sugars and has different subtypes depending on the position and number of bonded sulfate groups. However, the effect of each subtype on myogenic differentiation remains unclear. In this study, we spiked cultures of C₂C12 myoblasts, cells which are capable of undergoing skeletal muscle differentiation, with one of five types of CS (CS-A, -B, -C, -D, or -E) and induced differentiation over a fixed time. After immunostaining of the formed myotubes with an anti-MHC antibody, we counted the number of nuclei in the myotubes and then calculated the fusion index (FI) as a measure of myotube differentiation. The FI values of all the CS-treated groups were lower than the FI value of the control group, especially the group treated with CS-E, which displayed notable suppression of myotube formation. To confirm that the sugar chain in CS-E is important in the suppression of differentiation, chondroitinase ABC (ChABC), which catabolizes CS, was added to the media. The addition of ChABC led to the degradation of CS-E, and neutralized the suppression of myotube formation by CS-E. Collectively, it can be concluded that the degree of suppression of differentiation depends on the subtype of CS and that CS-E strongly suppresses myogenic differentiation. We conclude that the CS sugar chain has inhibitory action against myoblast cell fusion.

https://www.mdpi.com/1660-3397/14/10/193/pdf

Degree of Suppression of Mouse Myoblast Cell Line C₂C12 Differentiation Varies According to Chondroitin Sulfate Subtype.

Glycosaminoglycans (GAG) from the velvet antlers of Sika deer (Cervus nippon) at the different growing stages (Fukurozuno, Anshi, and Santajo) of bred and wild deer were isolated and their concentrations and sulfation patterns were analyzed. GAG were digested with chondroitinase ABC, ACI, heparinase-I and -III, and keratanase-II into the corresponding repeating disaccharides of chondroitin sulfate (CS), dermatan sulfate (DS), hyaluronan, heparan sulfate (HS), and keratan sulfate. Cartilaginous tissues contained CS-DS at high concentrations with an almost equal ratio of 4- and 6-sulfates, while 4-sulfate-type CS-DS predominantly occupied ossified tissues, but at low concentrations. High O- and N-sulfation degrees of HS correspond to high ossification. Dynamic quantitative changes in CS-DS and compositional changes in CS-DS and HS were closely associated with the mineralization of deer antlers.

Naoko Takeda-Okuda

Papers

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block.

Synthesis of chondroitin sulfate CC and DD tetrasaccharides and interactions with 2H6 and LY111.

Degree of Suppression of Mouse Myoblast Cell Line C₂C12 Differentiation Varies According to Chondroitin Sulfate Subtype.

Compositional analysis of the glycosaminoglycan family in velvet antlers of Sika deer ( Cervus nippon ) at different growing stages

Synthesis of a biotinylated keratan sulfate tetrasaccharide composed of dimeric Galβ1-4GlcNAc6Sβ