Biological evaluation and molecular modeling of peptidomimetic compounds as inhibitors for O-GlcNAc transferase (OGT)
| Autor: | Thalita G. Barros, Luiz A.P. Flores-Junior, Luiza R.S. Dias, Suraby O. Albuquerque, Wagner B. Dias, Hector F. Loponte, Estela M.F. Muri, Adriane R. Todeschini, Eldio Gonçalves dos Santos, Pedro H.R. de A. Azevedo, Sergio Pinheiro, Camilo Henrique da Silva Lima |
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| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Models Molecular Cell signaling Glycosylation Molecular model Peptidomimetic Pharmaceutical Science 02 engineering and technology 021001 nanoscience & nanotechnology N-Acetylglucosaminyltransferases 030226 pharmacology & pharmacy Acetylglucosamine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enzyme Biochemistry chemistry Transcription (biology) Transferase Peptidomimetics Binding site 0210 nano-technology |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 154 |
| ISSN: | 1879-0720 |
| Popis: | The vital enzyme O-linked β-N-acetylglucosamine transferase (OGT) catalyzes the O-GlcNAcylation of intracellular proteins coupling the metabolic status to cellular signaling and transcription pathways. Aberrant levels of O-GlcNAc and OGT have been linked to metabolic diseases as cancer and diabetes. Here, a new series of peptidomimetic OGT inhibitors was identified highlighting the compound LQMed 330, which presented better IC50 compared to the most potent inhibitors found in the literature. Molecular modeling study of selected inhibitors into the OGT binding site provided insight into the behavior by which these compounds interact with the enzyme. The results obtained in this study provided new perspectives on the design and synthesis of highly specific OGT inhibitors. |
| Databáze: | OpenAIRE |
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