Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase
Abstract
Simplified analogues of the potent human amylase inhibitor montbretin A were synthesised and shown to bind tightly, KI = 60 and 70 nM, with improved specificity over medically relevant glycosidases, making them promising candidates for controlling blood glucose. Crystallographic analysis confirmed similar binding modes and identified new active site interactions.
- Authors:
-
- Department of Chemistry, University of British Columbia, Vancouver BC, Canada V6T 1Z1
- Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver BC, Canada V6T 1Z3
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); Canadian Glycomics Network/Networks of Centres of Excellence; USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
- OSTI Identifier:
- 1572100
- Alternate Identifier(s):
- OSTI ID: 1624978
- Grant/Contract Number:
- AC02-76SF00515
- Resource Type:
- Published Article
- Journal Name:
- Chemical Science
- Additional Journal Information:
- Journal Name: Chemical Science Journal Volume: 10 Journal Issue: 48; Journal ID: ISSN 2041-6520
- Publisher:
- Royal Society of Chemistry (RSC)
- Country of Publication:
- United Kingdom
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; Chemistry
Citation Formats
Tysoe, Christina R., Caner, Sami, Calvert, Matthew B., Win-Mason, Anna, Brayer, Gary D., and Withers, Stephen G. Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase. United Kingdom: N. p., 2019.
Web. doi:10.1039/C9SC02610J.
Tysoe, Christina R., Caner, Sami, Calvert, Matthew B., Win-Mason, Anna, Brayer, Gary D., & Withers, Stephen G. Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase. United Kingdom. https://doi.org/10.1039/C9SC02610J
Tysoe, Christina R., Caner, Sami, Calvert, Matthew B., Win-Mason, Anna, Brayer, Gary D., and Withers, Stephen G. Wed .
"Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase". United Kingdom. https://doi.org/10.1039/C9SC02610J.
@article{osti_1572100,
title = {Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase},
author = {Tysoe, Christina R. and Caner, Sami and Calvert, Matthew B. and Win-Mason, Anna and Brayer, Gary D. and Withers, Stephen G.},
abstractNote = {Simplified analogues of the potent human amylase inhibitor montbretin A were synthesised and shown to bind tightly, KI = 60 and 70 nM, with improved specificity over medically relevant glycosidases, making them promising candidates for controlling blood glucose. Crystallographic analysis confirmed similar binding modes and identified new active site interactions.},
doi = {10.1039/C9SC02610J},
journal = {Chemical Science},
number = 48,
volume = 10,
place = {United Kingdom},
year = {Wed Dec 11 00:00:00 EST 2019},
month = {Wed Dec 11 00:00:00 EST 2019}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1039/C9SC02610J
https://doi.org/10.1039/C9SC02610J
Other availability
Cited by: 3 works
Citation information provided by
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Web of Science
Figures / Tables:
Fig. 1: Structures of montbretin A and mini-MbA.
All figures and tables
(8 total)
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Figures / Tables found in this record:
Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.