Synthesis of Neu5Ac Oligosaccharides and Analogues by Transglycosylation and their Binding Properties as Ligands to MAG

Handbook of Carbohydrate-Modifying Biocatalysts

“…Apparently, trans-sialidase will easily recognize these modified structures. In contrast, STD-NMR studies showed that only the original trisaccharide 77 is a well binding substrate for MAG and the analogous structures 79 and 81 are not (Neubacher et al, 2006) (Fig. 13.18).…”

“…Treatment of various lactose and N-acetyllactosamine structures 72 (R 1 =SPh, R 2 =N 3 ; R 1 =R 2 =OH; R 1 =OAll, R 2 =OH; R 1 =OMe, R 2 =NHAc) with p-nitrophenyl sialylate 67 and trans-sialidase gave the corresponding trisaccharides 73 in 30-60% yield. Correspondingly, a b,1-3-linked isolactosamine precursor could be reacted with muraminyl sialylate 70 to give the trisaccharide in 30% yield (Neubacher et al, 2006) (Fig. 13.17).…”

Chemical Biology of Cell Surface Oligosaccharides

“…Finally, a third strategy is based on a new class of MOE analogs comprised of para-nitrophenyl glycosides of sialic acids with modified polyol chains (the C7 to C9 positions). The Thiem group recently showed that these compounds were readily transferred by the trans-sialidase of T. cruzi [106], and therefore systemic administration of such compounds in vivo should result in metabolic labeling of the parasites. Such glycosides, however, are probably refractory to the mammalian sialic acid machinery-if for no other reason than poor uptake by cells-promising highly specific display on the parasite.…”

Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries

“…TcTS, in particular, has a relaxed acceptor specificity 16 which has proved to be a useful tool with which to generate α-(2→3)-sialylated glycans for the study of carbohydrate recognition by E -selectin, 17 Toxoplasma gondii microneme protein 1, 18 and the Siglec family member MAG (myelin-associated glycoprotein). 19 It has also been exploited for the sialylation of (synthetic) T. cruzi mucin glycans 20 and for the resialylation of desialylated sheep erythrocytes, for instance. 21 Herein we report studies aimed at exploring the acceptor substrate binding site of recombinant T. cruzi trans -sialidase 22 using a series of small libraries of systematically modified glycans and a thiogalactoside-based combinatorial library.…”