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

Research output: Contribution to journalArticle

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

Fingerprint

Glucosidases
glucosidases
acarbose
Acarbose
amylases
Amylases
synthesis
glucan 1,4-alpha-maltohydrolase
Intestines
Rats
intestines
hypoglycemic agents
glucose
glycosidases
Glycoside Hydrolases
rats
Chromatography
Reaction products
Hypoglycemic Agents
chromatography

Keywords

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

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Food Science
  • Chemistry (miscellaneous)

Cite this

Enzymatic synthesis of a selective inhibitor for α-glucosidases : α-acarviosinyl-(1→9)-3-α-D-glucopyranosylpropen. / Lee, Young Su; Lee, Myoung Hee; Lee, Hee Seob; Lee, Seung Jae; Kim, Young Wan; Zhang, Ran; Withers, Stephen G.; Kwan, Soo Kim; Lee, Sung-Joon; Park, Kwan Hwa.

In: Journal of Agricultural and Food Chemistry, Vol. 56, No. 13, 09.07.2008, p. 5324-5330.

Research output: Contribution to journalArticle

Lee, Young Su ; Lee, Myoung Hee ; Lee, Hee Seob ; Lee, Seung Jae ; Kim, Young Wan ; Zhang, Ran ; Withers, Stephen G. ; Kwan, Soo Kim ; Lee, Sung-Joon ; Park, Kwan Hwa. / Enzymatic synthesis of a selective inhibitor for α-glucosidases : α-acarviosinyl-(1→9)-3-α-D-glucopyranosylpropen. In: Journal of Agricultural and Food Chemistry. 2008 ; Vol. 56, No. 13. pp. 5324-5330.
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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.",
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T1 - Enzymatic synthesis of a selective inhibitor for α-glucosidases

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AU - Lee, Myoung Hee

AU - Lee, Hee Seob

AU - Lee, Seung Jae

AU - Kim, Young Wan

AU - Zhang, Ran

AU - Withers, Stephen G.

AU - Kwan, Soo Kim

AU - Lee, Sung-Joon

AU - Park, Kwan Hwa

PY - 2008/7/9

Y1 - 2008/7/9

N2 - 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.

AB - 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.

KW - 3-α-D- glucopyranosylpropen

KW - Acarbose

KW - Inhibitor

KW - Maltogenic amylase from Thermus sp.

KW - Transglycosylation

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