Translating solution to solid phase glycosylation conditions

Abstract

Optimizing glycosylation conditions for automated glycan assembly is highly challenging, demand wasteful use of precious building blocks and rely on nontrivial analyses. We developed a semi-quantitative method for automated optimization...

Transport phenomena in solid phase synthesis supported by cross-linked polymer beads

“…44–46; for glycans see: ref. 22, 24 and 32; Bakhatan et al 32 recently reported dimer formation with a cycle time of 8 min).…”

“…Film diffusion resistance may be minimal on particle sizes of 35-100 μm". 54 32 recently reported dimer formation with a cycle time of 8 min). c Obtained from equipment manufacturers (taking the upper limit).…”

“…44–46; for glycans see: ref. 22, 24 and 32; Bakhatan et al 32 recently reported dimer formation with a cycle time of 8 min).cObtained from equipment manufacturers (taking the upper limit). 47–50 The scale could reach 3 kg for nucleic acids and peptides (the lab scale is hundreds of milligrams), while for glycans, the typical amount of product is 2 mg.…”

“…Recent strategies to achieve reaction acceleration included microwave radiation, 24,29,30 dual temperature control systems, 24 pre-heating the reagents, 28,31 and highshear mixing methods. [25][26][27]32 However, little attention has been paid to formal modeling and understanding the transport phenomena behind such technological developments.…”

Synthesis of a heparan sulfate tetrasaccharide using automated glycan assembly

“…Semi-automated temperature-controlled experiments aid in selecting reaction temperatures for thioglycoside building blocks to be used in AGA synthesisers. 32,33 Identification of the optimal reaction temperature drastically improves the efficiency of AGA processes, as illustrated in the context of a β-(1-4) glucan synthesis. 32 Activation experiments with glycosyl phosphates, in the absence of a nucleophile, at different temperatures were carried out in the AGA reactor (Table 1).…”