| Title | Enzymatic Synthesis of a Selective Inhibitor for alpha-Glucosidases: alpha-Acarviosinyl-(1-->9)-3-alpha-d-glucopyranosylpropen. | | Author(s) | Lee YS, Lee MH, Lee HS, Lee SJ, Kim YW, Zhang R, Withers SG, Kim KS, Lee SJ, Park KH | | Institution | Center for Agricultural Biomaterials and School of Agriculture and Biotechnology, Seoul National University, Seoul 151-921, Korea, Department of Food and Nutrition, Pusan National University, Pusan 609-735, Korea, Department of Food and Biotechnology, Korea University, Jochiwon 339-700, Korea, Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z4, Canada, Department of Chemistry, College of Science, Yonsei University, Seoul 120-749, Korea, and Division of Food Bioscience and Technology, Korea University, Seoul 136-713, Korea parkkh@snu.ac.kr. | | Source | J Agric Food Chem 2008 Jun 14. | | Abstract | Here, we describe the enzymatic synthesis of novel inhibitors using acarviosine-glucose as a donor and 3-alpha- d-glucopyranosylpropen (alphaGP) as an acceptor. Maltogenic amylase from Thermus sp. (ThMA) catalyzed the transglycosylation of the acarviosine moiety to alphaGP. 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 alphaGP, which correspond to C-4 and C-6 of glucose. Both inhibited rat intestine alpha-glucosidase competitively but displayed a mixed-type inhibition mode against human pancreatic alpha-amylase. The alpha-acarviosinyl-(1-->7)-3-alpha- d-glucopyranosylpropen showed weaker inhibition potency than acarbose against both alpha-glycosidases. In contrast, the alpha-acarviosinyl-(1-->9)-3-alpha- d-glucopyranosylpropen exhibited a 3.0-fold improved inhibition potency against rat intestine alpha-glucosidase with 0.3-fold inhibition potency against human pancreatic alpha-amylase relative to acarbose. In conclusion, alpha-acarviosinyl-(1-->9)-3-alpha- d-glucopyranosylpropen is a novel alpha-glucosidase-selective inhibitor with 10-fold enhanced selectivity toward alpha-glucosidase over alpha-amylase relative to acarbose, and it could be applied as a potent hypoglycemic agent. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18553919 |
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