Glycosyl-transferase catalyzed assemblage of sialyl-lewis x -saccharopeptides

Substrate and donor specificity of glycosyl transferases

“…Glucosamine derivatives tolerated as substrates by b(1-4)galactosyl transferase 84 charged residues (entries 4, 5) or sulfonamides (entry 6) [50] is well tolerated. Bulky polar monosaccharides (entry 8) are also easily sialylated in the expected manner [46]. Thus, libraries of sialylated type II sugars-the immediate precursors of the sialyl-Lewis x -tetrasaccharides-are produced rapidly with good overall yields.…”

“…b(1-4)Galactosyl transferase shows also an unexpectedly broad tolerance towards non-natural N-acyl residues of the acceptor substrate [36,41,46]. Preparatively useful yields have been obtained with bulky (entries 10,13,14) or charged substituents (entries 11, 12).…”

“…Small (entry 2) or bulky aromatic residues (entries 3, 7) are accepted. In addition, charged substituents (entry 5) [52], a bulky polar monosaccharide (entry 8) [46] or even a sulfonamide (entry 6) [52] are tolerated. Moreover (see Table 3b), the concomitant replacement of the natural N-acetyl group and the L-fucose donor by non-natural N-acyl moieties and D-arabinose (entries 9a-12a) or L-galactose (entries 9b-12b), respectively, is well accepted by FucT VI [53].…”

“…The natural N-acetyl group can for example be replaced by aromatic or heteroaromatic (entries 5, 6) or charged amide residues (entries 3, 4) [55]. Even sulfonamides (entry 7) and bulky saccharides (entry 8) do not impede the proper sialylation [46]. Table 6.…”

Saccharide–Peptide Hybrids

“…Ohrlein have prepared mimetics in which the acetamido group of the central glucosamine was replaced by methyl glycopyranosiduronamides [ 60,631. Disaccharide mimetics of type 73 were accepted as substrates by the enzymes 2,3-sialyltransferase, p( 1 + 4)galactosyltransferase and fucosyltransferases I11 and IV, so enzymatic synthesis of sialyl LewisX and sialyl Lewisa mimetics such 84 (Scheme 12) was feasible.…”