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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 |
| Pages: | 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 |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| 2019_Fischer_high-consistency.pdf | 5.88 MB | Adobe PDF |  View/Open |
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