Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase

Simplified analogues of the potent human amylase inhibitor montbretin A were synthesised and shown to bind tightly, K(I) = 60 and 70 nM, with improved specificity over medically relevant glycosidases, making them promising candidates for controlling blood glucose. Crystallographic analysis confirmed...

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Detalles Bibliográficos
Autores principales: Tysoe, Christina R., Caner, Sami, Calvert, Matthew B., Win-Mason, Anna, Brayer, Gary D., Withers, Stephen G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2019
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069248/
https://www.ncbi.nlm.nih.gov/pubmed/32206255
http://dx.doi.org/10.1039/c9sc02610j
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author Tysoe, Christina R.
Caner, Sami
Calvert, Matthew B.
Win-Mason, Anna
Brayer, Gary D.
Withers, Stephen G.
author_facet Tysoe, Christina R.
Caner, Sami
Calvert, Matthew B.
Win-Mason, Anna
Brayer, Gary D.
Withers, Stephen G.
author_sort Tysoe, Christina R.
collection PubMed
description Simplified analogues of the potent human amylase inhibitor montbretin A were synthesised and shown to bind tightly, K(I) = 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.
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spelling pubmed-70692482020-03-23 Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase Tysoe, Christina R. Caner, Sami Calvert, Matthew B. Win-Mason, Anna Brayer, Gary D. Withers, Stephen G. Chem Sci Chemistry Simplified analogues of the potent human amylase inhibitor montbretin A were synthesised and shown to bind tightly, K(I) = 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. Royal Society of Chemistry 2019-10-18 /pmc/articles/PMC7069248/ /pubmed/32206255 http://dx.doi.org/10.1039/c9sc02610j Text en This journal is © The Royal Society of Chemistry 2019 http://creativecommons.org/licenses/by-nc/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0)
spellingShingle Chemistry
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
title Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase
title_full Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase
title_fullStr Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase
title_full_unstemmed Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase
title_short Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase
title_sort synthesis of montbretin a analogues yields potent competitive inhibitors of human pancreatic α-amylase
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069248/
https://www.ncbi.nlm.nih.gov/pubmed/32206255
http://dx.doi.org/10.1039/c9sc02610j
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