1998 Volume 123 Issue 3 Pages 508-515
We performed chemo-enzymatic transformation of maltooligosaccharides into both endmodified oligosaccharidonolactones of potential use as substrate analogue inhibitors for mammalian α-amylases. Enzymatic modification of the non-reducing end glucosyl residue of the maltooligosaccharide was first performed by transglycosylation with β-D-galactosidase from Bacillus circulans. When maltotriose and maltotetraose were the acceptors, the enzyme regioselectively synthesized 43-O-β-D-galactosyl maltotriose (LG3) and 44-O-β-D-galactosyl maltotetraose (LG4) from lactose as a donor. LG4 was further selectively hydrolyzed with a specific a-amylase to afford 42-O-β-D-galactosyl maltose (LG2). The anomer hydroxyl groups of LG2 and LG3 were chemically oxidized to give the corresponding lactones, 42-O-β-D-galactosyl maltobionolactone (LG2O) and 43-O-β-D-galactosyl maltotrionolactone (LG3O), respectively. LG2O and LG3O, which are competitive inhibitors for mammalian α-amylases, exhibited Ki values of the order of 2.8-18.0 μM, with p-nitrophenyl α-maltopentaoside (G5P) as the substrate. On 1H-NMR analysis, these oligosaccharidonolactones were shown to be transformed into the corresponding aldonic acid forms with time in an aqueous solution. In this case, the lactone form was essential for the occurrence of the α-amylase inhibitor.
