Structure-based virtual screening: an application to human topoisomerase II alpha
| العنوان: | Structure-based virtual screening: an application to human topoisomerase II alpha |
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| المؤلفون: | Serge Christmann-Franck, Serge Fermandjian, P. Arsène Der Garabedian, Rémy Hoffmann, Anne Goupil-Lamy, Olivier Mauffret, Hugues-Olivier Bertrand |
| المساهمون: | Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Accelrys, Biochimie des signaux régulateurs cellulaires et moléculaires (BSRCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC) |
| المصدر: | Journal of Medicinal Chemistry Journal of Medicinal Chemistry, 2004, 47 (27), pp.6840-53. ⟨10.1021/jm049745w⟩ Journal of Medicinal Chemistry, American Chemical Society, 2004, 47 (27), pp.6840-53. ⟨10.1021/jm049745w⟩ |
| بيانات النشر: | HAL CCSD, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Models, Molecular, Molecular model, MESH: Antigens, Neoplasm, MESH: Amino Acid Sequence, 0302 clinical medicine, Protein structure, Drug Discovery, Topoisomerase II Inhibitors, Enzyme Inhibitors, 0303 health sciences, biology, Molecular Structure, Chemistry, 3. Good health, DNA-Binding Proteins, Biochemistry, Enzyme inhibitor, MESH: Enzyme Inhibitors, 030220 oncology & carcinogenesis, Molecular Medicine, medicine.symptom, Pharmacophore, Dimerization, MESH: Models, Molecular, Molecular Sequence Data, MESH: Molecular Structure, MESH: Sequence Alignment, 03 medical and health sciences, Antigens, Neoplasm, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, MESH: Templates, Genetic, 030304 developmental biology, MESH: DNA Topoisomerases, Type II, Eukaryotic, Virtual screening, Binding Sites, MESH: Humans, MESH: Molecular Sequence Data, Topoisomerase, Templates, Genetic, DNA Topoisomerases, Type II, Mechanism of action, Structural biology, MESH: Binding Sites, MESH: Dimerization, biology.protein, Sequence Alignment, MESH: DNA-Binding Proteins |
| الوصف: | International audience; The eukaryotic topoisomerase II is involved in several vital processes, such as replication, transcription, and recombination. Many compounds interfering with the catalytic action of this enzyme are efficient in human cancer chemotherapy. We applied a methodology combining molecular modeling and virtual screening techniques to identify human topoisomerase II alphainhibitors. Data from structural biology and enzymatic assays together with a good background on the enzyme mechanism of action were helpful in the approach. A human topoisomerase II alpha model provided an insight into the structural features responsible for the activity of the enzyme. A protocol comprising several substructural and protein structure-based three-dimensional pharmacophore filters enabled the successful retrieving of inhibitors of the enzyme from large databases of compounds, thus validating the approach. A subset of protein structural features required for the enzyme inhibition at the protein-DNA interface were identified and incorporated into the pharmacophore models. Compounds sharing a DNA-intercalating chromophore and a moiety interfering with the protein active site emerged as good inhibitors. |
| اللغة: | English |
| تدمد: | 0022-2623 1520-4804 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c49caaaacf4f3f9c5e257ea1e9b183fc https://hal.science/hal-00284749 |
| رقم الأكسشن: | edsair.doi.dedup.....c49caaaacf4f3f9c5e257ea1e9b183fc |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 00222623 15204804 |
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