Enzymatic synthesis of a selective inhibitor for α-glucosidases: α-acarviosinyl-(1→9)-3-α-D-glucopyranosylpropen

Here, we describe the enzymatic synthesis of novel inhibitors using acarviosine-glucose as a donor and 3-α-D-glucopyranosylpropen (αGP) as an acceptor. Maltogenic amylase from Thermussp. (ThMA) catalyzed the transglycosylation of the acarviosine moiety to aGP. The two major reaction products were isolated using chromatographies. Structural analyses revealed that acarviosine was transferred to either C-7 or C-9 of the αGP, which correspond to C-4 and C-6 of glucose. Both inhibited rat intestine α-glucosidase competitively but displayed a mixed-type inhibition mode against human pancreatic α-amylase. The α-acarviosinyl-(1→7)-3- α-D-glucopyranosylpropen showed weaker inhibition potency than acarbose against both α-glycosidases. In contrast, the α-acarviosinyl- (1→9)-3-α-D-glucopyranosylpropen exhibited a 3.0-fold improved inhibition potency against rat intestine α-glucosidase with 0.3-fold inhibition potency against human pancreatic α-amylase relative to acarbose. In conclusion, α-acarviosinyl-(1→9)-3-α-D- glucopyranosylpropen is a novel α-glucosidase-selective inhibitor with 10-fold enhanced selectivity toward α-glucosidase over α-amylase relative to acarbose, and it could be applied as a potent hypoglycemic agent.