Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono-, Di-, and Trifluorinated d-Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition

[Image: see text] Glucokinase phosphorylated a series of C-1 fluorinated α-d-gluco-heptuloses. These phosphorylated products were discovered to be inhibitors of α-phosphomannomutase/phosphoglucomutase (αPMM/PGM) and β-phosphoglucomutase (βPGM). Inhibition potency with both mutases inversely correlat...

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Autores principales: Zhu, Jian-She, Stiers, Kyle M., Winter, Sherany M., Garcia, Anthony D., Versini, Antoine F., Beamer, Lesa J., Jakeman, David L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547622/
https://www.ncbi.nlm.nih.gov/pubmed/31179410
http://dx.doi.org/10.1021/acsomega.9b00008
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author Zhu, Jian-She
Stiers, Kyle M.
Winter, Sherany M.
Garcia, Anthony D.
Versini, Antoine F.
Beamer, Lesa J.
Jakeman, David L.
author_facet Zhu, Jian-She
Stiers, Kyle M.
Winter, Sherany M.
Garcia, Anthony D.
Versini, Antoine F.
Beamer, Lesa J.
Jakeman, David L.
author_sort Zhu, Jian-She
collection PubMed
description [Image: see text] Glucokinase phosphorylated a series of C-1 fluorinated α-d-gluco-heptuloses. These phosphorylated products were discovered to be inhibitors of α-phosphomannomutase/phosphoglucomutase (αPMM/PGM) and β-phosphoglucomutase (βPGM). Inhibition potency with both mutases inversely correlated to the degree of fluorination. Structural analysis with αPMM demonstrated the inhibitor binding to the active site, with the phosphate in the phosphate binding site and the anomeric hydroxyl directed to the catalytic site.
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spelling pubmed-65476222019-06-05 Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono-, Di-, and Trifluorinated d-Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition Zhu, Jian-She Stiers, Kyle M. Winter, Sherany M. Garcia, Anthony D. Versini, Antoine F. Beamer, Lesa J. Jakeman, David L. ACS Omega [Image: see text] Glucokinase phosphorylated a series of C-1 fluorinated α-d-gluco-heptuloses. These phosphorylated products were discovered to be inhibitors of α-phosphomannomutase/phosphoglucomutase (αPMM/PGM) and β-phosphoglucomutase (βPGM). Inhibition potency with both mutases inversely correlated to the degree of fluorination. Structural analysis with αPMM demonstrated the inhibitor binding to the active site, with the phosphate in the phosphate binding site and the anomeric hydroxyl directed to the catalytic site. American Chemical Society 2019-04-18 /pmc/articles/PMC6547622/ /pubmed/31179410 http://dx.doi.org/10.1021/acsomega.9b00008 Text en Copyright © 2019 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Zhu, Jian-She
Stiers, Kyle M.
Winter, Sherany M.
Garcia, Anthony D.
Versini, Antoine F.
Beamer, Lesa J.
Jakeman, David L.
Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono-, Di-, and Trifluorinated d-Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition
title Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono-, Di-, and Trifluorinated d-Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition
title_full Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono-, Di-, and Trifluorinated d-Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition
title_fullStr Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono-, Di-, and Trifluorinated d-Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition
title_full_unstemmed Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono-, Di-, and Trifluorinated d-Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition
title_short Synthesis, Derivatization, and Structural Analysis of Phosphorylated Mono-, Di-, and Trifluorinated d-Gluco-heptuloses by Glucokinase: Tunable Phosphoglucomutase Inhibition
title_sort synthesis, derivatization, and structural analysis of phosphorylated mono-, di-, and trifluorinated d-gluco-heptuloses by glucokinase: tunable phosphoglucomutase inhibition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547622/
https://www.ncbi.nlm.nih.gov/pubmed/31179410
http://dx.doi.org/10.1021/acsomega.9b00008
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