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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
Published in: Molecules
Volume(Issue): 24
Issue: 7
Pages: 1322
Issue Date: 2019
Publisher / Ed. Institution: MDPI
ISSN: 1420-3049
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.
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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