دورية أكاديمية
Design and synthesis of unprecedented 9- and 10-membered cyclonucleosides with PRMT5 inhibitory activity.
| العنوان: | Design and synthesis of unprecedented 9- and 10-membered cyclonucleosides with PRMT5 inhibitory activity. |
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| المؤلفون: | Kawamura S; Discovery Chemistry, Merck & Co., Inc., Boston, MA 02115, United States. Electronic address: shuhei.kawamura@merck.com., Palte RL; Computational and Structural Chemistry, Merck & Co., Inc., Boston, MA 02115, United States., Kim HY; NMR Structure Elucidation, Process and Analytical Chemistry, Merck & Co., Inc., Boston, MA 02115, United States., Saurí J; NMR Structure Elucidation, Process and Analytical Chemistry, Merck & Co., Inc., Boston, MA 02115, United States., Sondey C; Quantitative Biosciences, Merck & Co., Inc., Boston, MA 02115, United States., Mansueto MS; Quantitative Biosciences, Merck & Co., Inc., Boston, MA 02115, United States., Altman MD; Computational and Structural Chemistry, Merck & Co., Inc., Boston, MA 02115, United States., Machacek MR; Discovery Chemistry, Merck & Co., Inc., Boston, MA 02115, United States. |
| المصدر: | Bioorganic & medicinal chemistry [Bioorg Med Chem] 2022 Jul 15; Vol. 66, pp. 116820. Date of Electronic Publication: 2022 May 14. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: England NLM ID: 9413298 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3391 (Electronic) Linking ISSN: 09680896 NLM ISO Abbreviation: Bioorg Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Original Publication: Oxford : New York : Pergamon Press, c1993- |
| مواضيع طبية MeSH: | Adaptor Proteins, Signal Transducing*/metabolism , Protein-Arginine N-Methyltransferases*/chemistry |
| مستخلص: | Synthesis of medium-sized rings is known to be challenging due to high transannular strain especially for 9- and 10-membered rings. Herein we report design and synthesis of unprecedented 9- and 10-membered purine 8,5'-cyclonucleosides as the first cyclonucleoside PRMT5 inhibitors. The cocrystal structure of PRMT5:MEP50 in complex with the synthesized 9-membered cyclonucleoside 1 revealed its binding mode in the SAM binding pocket of PRMT5. (Copyright © 2022 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Cyclonucleoside; Medicinal chemistry; Molecular modeling; Nucleoside; PRMT5; PRMT5 inhibitor; X-ray crystallography |
| المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) EC 2.1.1.319 (Protein-Arginine N-Methyltransferases) |
| تواريخ الأحداث: | Date Created: 20220520 Date Completed: 20220602 Latest Revision: 20220705 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.bmc.2022.116820 |
| PMID: | 35594650 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1464-3391 |
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| DOI: | 10.1016/j.bmc.2022.116820 |