Automated solution-phase multiplicative synthesis of complex glycans up to a 1,080-mer

Synthesis of Regioselective Carbohydrates Building Blocks by Heterogeneous Engineered Biocatalysts

“…Palomo in combination with the new technologies based on the solid-phase synthesis of complex oligosaccharides, for example, for vaccines preparation. [6] Due to the high regioand enantioselectivity of the enzymes, lipases represent a promising alternative to chemical methods to overcome all these drawbacks. Lipases are quite particular enzymes with a complex catalytic mechanism, who manages their catalysis on the basis of the conformational changes between a 'closed' and an 'open' form.…”

Automating Glycan Assembly in Solution

“…Scientists’ understanding of structure–function relationships , involving carbohydratesone of the essential biomacromolecules in living systemsis not so detailed as those relating to DNA/RNA and proteins. Consequently, carbohydrates are far from widely used in the development of new therapeutics and diagnostics or in materials science.…”

“…Recently, Ye and co-workers have reported a dual-mode glycan synthesizer (Figure ) based on the automation of solution-phase-based, multicomponent, one-pot chemical glycosylations (Figure a) in which several glycosyl building blocks are preactivated, using either chemical- or light-promoted protocols before reacting sequentially to produce sequence-defined oligosaccharides as the main products. This automated synthesizer, which (1) uses stoichiometric amounts of glycosyl building blocks and (2) monitors the progress of reactions directly employing online HPLC, can be carried out on a gram scale, thus overcoming some of the drawbacks of previously reported automated synthesizers.…”

“…In addition to the successful assembly of a library of linear and branched oligosaccharides, this automated synthesizer can execute the production of polysaccharides consisting of up to 1080 monosaccharide residues by employing a multiplicative synthetic strategy (Figure c). Although suffering from low reactivities and steric hindrance during large-fragment couplings, as well as difficulties in the global deprotection of 2161 protecting groups and purification of the final product, Ye and co-workers managed to accomplish the synthesis after several rounds of optimization of reaction and separation conditions. The fully deprotected 1080-mer α-1,5-arabinan (142.8 kDa) with 4320 stereogenic centers not only marks the longest and largest ever-made homogeneous polysaccharide in the history of carbohydrate chemistrya bold step in comparison with the previous syntheses − of large glycans using either manual or automated protocolsbut also raises the chemical syntheses of biomacromolecules to a completely new technical level that reaches far beyond the records chalked up already in the production of polynucleotides (up to 200-mer) and polypeptides (up to 472-mer).…”

“…was involved in the analysis of naturally occurring polysaccharides (gum arabic) during his Ph.D. studies at Edinburgh in the 1960s at which time making disaccharides was a suitable research project for a Ph.D. candidate to undertake. It is more than surprising and encouraging for us to find out that Ye and co-workers are now able to demonstrate how far carbohydrate chemists can push the envelope in glycan synthesis, enabled by the ingenious design and invention of an automated solution-phase synthesizer. Besides the superiority of the protocol, another merit of the current automated platform is the potential to integrate other strategies − employing one-pot transformations of carbohydrates in the most commonly used solution phase.…”