Novel Hydrazine Molecules as Tools To Understand the Flexibility of Vascular Adhesion Protein-1 Ligand-Binding Site: Toward More Selective Inhibitors
| العنوان: | Novel Hydrazine Molecules as Tools To Understand the Flexibility of Vascular Adhesion Protein-1 Ligand-Binding Site: Toward More Selective Inhibitors |
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| المؤلفون: | Ulla Pentikäinen, Elisa M. Nurminen, Ferenc Fülöp, László Lázár, Marjo Pihlavisto, Olli T. Pentikäinen |
| المصدر: | Journal of Medicinal Chemistry. 54:2143-2154 |
| بيانات النشر: | American Chemical Society (ACS), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Monoamine Oxidase Inhibitors, Protein Conformation, Monoamine oxidase, CHO Cells, Molecular Dynamics Simulation, Ligands, Substrate Specificity, Structure-Activity Relationship, Cricetulus, Cricetinae, Drug Discovery, Animals, Humans, Moiety, Hydrazine (antidepressant), Monoamine Oxidase, Binding Sites, Chemistry, Methylation, Adhesion, bacterial infections and mycoses, In vitro, Rats, respiratory tract diseases, Hydrazines, Biochemistry, Molecular Medicine, Amine gas treating, Amine Oxidase (Copper-Containing), Selectivity, Cell Adhesion Molecules |
| الوصف: | Vascular adhesion protein-1 (VAP-1) belongs to a family of amine oxidases. It plays a role in leukocyte trafficking and in amine compound metabolism. VAP-1 is linked to various diseases, such as Alzheimer's disease, psoriasis, depression, diabetes, and obesity. Accordingly, selective inhibitors of VAP-1 could potentially be used to treat those diseases. In this study, eight novel VAP-1 hydrazine derivatives were synthesized and their VAP-1 and monoamine oxidase (MAO) inhibition ability was determined in vitro. MD simulations of VAP-1 with these new molecules reveal that the VAP-1 ligand-binding pocket is flexible and capable of fitting substantially larger ligands than was previously believed. The increase in the size of the VAP-1 ligands, together with the methylation of the secondary nitrogen atom of the hydrazine moiety, improves the VAP-1 selectivity over MAO. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc7f75a89c6690fb5a419ecef9e6155d https://doi.org/10.1021/jm200059p |
| رقم الأكسشن: | edsair.doi.dedup.....dc7f75a89c6690fb5a419ecef9e6155d |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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