Yoon Seung-Heon, Robyt John F
Laboratory of Carbohydrate Chemistry and Enzymology, Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
Carbohydr Res. 2003 Sep 10;338(19):1969-80. doi: 10.1016/s0008-6215(03)00293-3.
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 alpha-amylases: Aspergillus oryzae, Bacillus amyloliquefaciens, human salivary, and porcine pancreatic alpha-amylases. The three inhibitors showed mixed, noncompetitive inhibition, for all four alpha-amylases. The acarbose inhibition constants, Ki, for the four alpha-amylases were 270, 13, 1.27, and 0.80 microM, 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 alpha-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 alpha-amylase inhibitors.
通过环糊精葡糖基转移酶与环麦芽六糖和阿卡波糖反应制备了阿卡波糖类似物，4IV-麦芽六糖基阿卡波糖（G6-Aca）和4IV-麦芽十二糖基阿卡波糖（G12-Aca）。研究了阿卡波糖及这两种阿卡波糖类似物对四种不同α-淀粉酶的抑制动力学，这四种α-淀粉酶分别为米曲霉、解淀粉芽孢杆菌、人唾液和猪胰α-淀粉酶。对于所有四种α-淀粉酶，这三种抑制剂均表现出混合型非竞争性抑制。阿卡波糖对这四种α-淀粉酶的抑制常数Ki分别为270、13、1.27和0.80微摩尔；G6-Aca的Ki值分别为33、37、14和7纳摩尔；G12-Aca的Ki常数分别为59、81、18和11纳摩尔。G6-Aca和G12-Aca类似物是所观察到的最有效的α-淀粉酶抑制剂，其Ki值比阿卡波糖强1至3个数量级，而阿卡波糖本身比其他已知的α-淀粉酶抑制剂强1至3个数量级。
