High consistency of structure-based design and x-ray crystallography : design, synthesis, kinetic evaluation and crystallographic binding mode determination of biphenyl-N-acyl-β-D-glucopyranosylamines as glycogen phosphorylase inhibitors

Fischer, Thomas; Koulas, Symeon M.; Tsagkarakou, Anastasia S.; Kyriakis, Efthimios; Stravodimos, George A.; Skamnaki, Vassiliki T.; Liggri, Panagiota G.V.; Zographos, Spyros E.; Riedl, Rainer; Leonidas, Demetres D.

doi:10.3390/molecules24071322

Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-19486

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	High consistency of structure-based design and x-ray crystallography : design, synthesis, kinetic evaluation and crystallographic binding mode determination of biphenyl-N-acyl-β-D-glucopyranosylamines as glycogen phosphorylase inhibitors
Authors:	Fischer, Thomas Koulas, Symeon M. Tsagkarakou, Anastasia S. Kyriakis, Efthimios Stravodimos, George A. Skamnaki, Vassiliki T. Liggri, Panagiota G.V. Zographos, Spyros E. Riedl, Rainer Leonidas, Demetres D.
et. al:	No
DOI:	10.3390/molecules24071322 10.21256/zhaw-19486
Published in:	Molecules
Volume(Issue):	24
Issue:	7
Page(s):	1322
Issue Date:	2019
Publisher / Ed. Institution:	MDPI
ISSN:	1420-3049 1433-1373
Language:	English
Subjects:	N-acyl-β-d-glucopyranosylamine; X-ray crystallography; Glycogen metabolism; Glycogen phosphorylase inhibitor; Structure-based design; Type 2 diabetes; Binding Site; Catalytic domain; Synthetic chemistry technique; Drug design; Enzyme inhibitor; Glucosamine; Glycogen phosphorylase; Human; Hydrogen bonding; Molecular model; Protein binding; Quantitative structure-activity relationship
Subject (DDC):	540: Chemistry
Abstract:	Structure-based design and synthesis of two biphenyl-N-acyl-β-d-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico-derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.
URI:	https://digitalcollection.zhaw.ch/handle/11475/19486
Fulltext version:	Published version
License (according to publishing contract):	CC BY 4.0: Attribution 4.0 International
Departement:	Life Sciences and Facility Management
Appears in collections:	Publikationen Life Sciences und Facility Management

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Fischer, T., Koulas, S. M., Tsagkarakou, A. S., Kyriakis, E., Stravodimos, G. A., Skamnaki, V. T., Liggri, P. G. V., Zographos, S. E., Riedl, R., & Leonidas, D. D. (2019). High consistency of structure-based design and x-ray crystallography : design, synthesis, kinetic evaluation and crystallographic binding mode determination of biphenyl-N-acyl-β-D-glucopyranosylamines as glycogen phosphorylase inhibitors. Molecules, 24(7), 1322. https://doi.org/10.3390/molecules24071322

Fischer, T. et al. (2019) ‘High consistency of structure-based design and x-ray crystallography : design, synthesis, kinetic evaluation and crystallographic binding mode determination of biphenyl-N-acyl-β-D-glucopyranosylamines as glycogen phosphorylase inhibitors’, Molecules, 24(7), p. 1322. Available at: https://doi.org/10.3390/molecules24071322.

T. Fischer et al., “High consistency of structure-based design and x-ray crystallography : design, synthesis, kinetic evaluation and crystallographic binding mode determination of biphenyl-N-acyl-β-D-glucopyranosylamines as glycogen phosphorylase inhibitors,” Molecules, vol. 24, no. 7, p. 1322, 2019, doi: 10.3390/molecules24071322.

FISCHER, Thomas, Symeon M. KOULAS, Anastasia S. TSAGKARAKOU, Efthimios KYRIAKIS, George A. STRAVODIMOS, Vassiliki T. SKAMNAKI, Panagiota G.V. LIGGRI, Spyros E. ZOGRAPHOS, Rainer RIEDL und Demetres D. LEONIDAS, 2019. High consistency of structure-based design and x-ray crystallography : design, synthesis, kinetic evaluation and crystallographic binding mode determination of biphenyl-N-acyl-β-D-glucopyranosylamines as glycogen phosphorylase inhibitors. Molecules. 2019. Bd. 24, Nr. 7, S. 1322. DOI 10.3390/molecules24071322

Fischer, Thomas, Symeon M. Koulas, Anastasia S. Tsagkarakou, Efthimios Kyriakis, George A. Stravodimos, Vassiliki T. Skamnaki, Panagiota G.V. Liggri, Spyros E. Zographos, Rainer Riedl, and Demetres D. Leonidas. 2019. “High Consistency of Structure-Based Design and X-Ray Crystallography : Design, Synthesis, Kinetic Evaluation and Crystallographic Binding Mode Determination of Biphenyl-N-Acyl-β-D-Glucopyranosylamines as Glycogen Phosphorylase Inhibitors.” Molecules 24 (7): 1322. https://doi.org/10.3390/molecules24071322.

Fischer, Thomas, et al. “High Consistency of Structure-Based Design and X-Ray Crystallography : Design, Synthesis, Kinetic Evaluation and Crystallographic Binding Mode Determination of Biphenyl-N-Acyl-β-D-Glucopyranosylamines as Glycogen Phosphorylase Inhibitors.” Molecules, vol. 24, no. 7, 2019, p. 1322, https://doi.org/10.3390/molecules24071322.