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

Young Su Lee, Myoung Hee Lee, Hee Seob Lee, Seung Jae Lee, Young Wan Kim, Ran Zhang, Stephen G. Withers, Soo Kim Kwan, Sung Joon Lee, Kwan Hwa Park

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9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5324-5330
Number of pages7
JournalJournal of agricultural and food chemistry
Volume56
Issue number13
DOIs
Publication statusPublished - 2008 Jul 9

Keywords

  • 3-α-D- glucopyranosylpropen
  • Acarbose
  • Inhibitor
  • Maltogenic amylase from Thermus sp.
  • Transglycosylation

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

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    Lee, Y. S., Lee, M. H., Lee, H. S., Lee, S. J., Kim, Y. W., Zhang, R., Withers, S. G., Kwan, S. K., Lee, S. J., & Park, K. H. (2008). Enzymatic synthesis of a selective inhibitor for α-glucosidases: α-acarviosinyl-(1→9)-3-α-D-glucopyranosylpropen. Journal of agricultural and food chemistry, 56(13), 5324-5330. https://doi.org/10.1021/jf703655k