Study of the inhibition of four alpha amylases by acarbose and its 4IV-α-maltohexaosyl and 4IV-α-maltododecaosyl analogues Original Research Article

Acarbose analogues, 4IV-maltohexaosyl acarbose (G6-Aca) and 4IV-maltododecaosyl acarbose (G12-Aca), were prepared by the reaction of cyclomaltodextrin glucanyltransferase with cyclomaltohexaose and acarbose. The inhibition kinetics of acarbose and the two acarbose analogues were studied for four different α-amylases: Aspergillus oryzae, Bacillus amyloliquefaciens, human salivary, and porcine pancreatic α-amylases. The three inhibitors showed mixed, noncompetitive inhibition, for all four α-amylases. The acarbose inhibition constants, Ki, for the four α-amylases were 270, 13, 1.27, and 0.80 μM, respectively; the Ki values for G6-Aca were 33, 37, 14, and 7 nM, respectively; and the G12-Aca Ki constants were 59, 81, 18, and 11 nM, respectively. The G6-Aca and G12-Aca analogues are the most potent α-amylase inhibitors observed, with Ki values one to three orders of magnitude more potent than acarbose, which itself was one to three orders of magnitude more potent than other known α-amylase inhibitors.