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Title: 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:
 [1];  [2];  [1];  [1];  [2]; ORCiD logo [1]
  1. Department of Chemistry, University of British Columbia, Vancouver BC, Canada V6T 1Z1
  2. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver BC, Canada V6T 1Z3
Publication Date:
Research Org.:
SLAC National Accelerator Lab., 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 = {2019},
month = {12}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1039/C9SC02610J

Figures / Tables:

Fig. 1 Fig. 1: Structures of montbretin A and mini-MbA.

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Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.