Comprehensive Modular Synthesis of Ganglioside Glycans and Evaluation of their Binding Affinities to Siglec-7 and Siglec-9.

In the present work, bacterial glycosyltransferases are utilized to construct ganglioside glycans in a convergent approach via a sugar‒nucleotide regeneration system and one-pot multienzyme reactions. Starting from β-lactoside enables the diversification of both the glycan moieties and the linkages in the lower α-arm and upper β-arm. Overall, a comprehensive panel of 24 natural a-series (GM3, GM2, GM1a, GD1a, GT1a, and fucosyl-GM1), b-series (GD3, GD2, GD1b, GT1b, and GQ1b), c-series (GT3, GT2, GT1c, GQ1c, and GP1c), α-series (GM1α, GD1aα, and GT1aα), and o-series (GA2, GA1, GM1b, GalNAc-GM1b, and GD1c) ganglioside glycans are prepared, which are suitable for biological studies and further applications.

Sugar nucleotide regeneration system for the synthesis of Bi- and triantennary N-glycans and exploring their activities against siglecs.

Enzymatic synthesis that is commenced by the sugar nucleotide regeneration system (SNRS) protocol can minimize 1) the consumption of exorbitant sugar nucleotides, 2) the amount of transferases required, and 3) byproduct feedback inhibition. In this study, LacNAc extensions/modifications of the N-linked mannose core were carried out efficiently with SNRS with high yields and purities on all branches in a uniform manner. In addition, we demonstrate that with SNRS, bacterial glycosyltransferases exhibit a wide acceptor tolerance for bi- and triantennary mannose core structures as substrates for target oligosaccharides.