Recent progress in fragment-based drug discovery facilitated by NMR spectroscopy
Considerable developments have been observed in fragment-based lead/drug discovery (FBLD/FBDD) recently, with four drugs approved and many others under investigation. Nuclear magnetic resonance (NMR) has gained increasing popularity in FBLD due to its intrinsic capability in characterizing protein-l...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co. Ltd.
2022-05-01
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| Series: | Magnetic Resonance Letters |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772516221000255 |
| _version_ | 1798005989618745344 |
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| author | Lei Wang Jia Gao Rongsheng Ma Yaqian Liu Mingqing Liu Fumei Zhong Jie Hu Shuju Li Jihui Wu Hualiang Jiang Jiahai Zhang Ke Ruan |
| author_facet | Lei Wang Jia Gao Rongsheng Ma Yaqian Liu Mingqing Liu Fumei Zhong Jie Hu Shuju Li Jihui Wu Hualiang Jiang Jiahai Zhang Ke Ruan |
| author_sort | Lei Wang |
| collection | DOAJ |
| description | Considerable developments have been observed in fragment-based lead/drug discovery (FBLD/FBDD) recently, with four drugs approved and many others under investigation. Nuclear magnetic resonance (NMR) has gained increasing popularity in FBLD due to its intrinsic capability in characterizing protein-ligand interactions in a large dynamic range of affinity, from weak hits to highly potent drugs. Here, we summarize NMR applications in fragment-based hit-to-lead evolution, including the construction of a fragment library, screening methods, spectra processing, and the delineation of the protein-ligand binding modes. These state-of-the-art NMR techniques have been exemplified in the discovery of inhibitors against multiple targets over the past five years, and they are expected to continue to provide new insights in the future. |
| first_indexed | 2024-04-11T12:47:46Z |
| format | Article |
| id | doaj.art-c2fc70698ead422fb2c1e436641197ab |
| institution | Directory Open Access Journal |
| issn | 2772-5162 |
| language | English |
| last_indexed | 2024-04-11T12:47:46Z |
| publishDate | 2022-05-01 |
| publisher | KeAi Communications Co. Ltd. |
| record_format | Article |
| series | Magnetic Resonance Letters |
| spelling | doaj.art-c2fc70698ead422fb2c1e436641197ab2022-12-22T04:23:18ZengKeAi Communications Co. Ltd.Magnetic Resonance Letters2772-51622022-05-0122107118Recent progress in fragment-based drug discovery facilitated by NMR spectroscopyLei Wang0Jia Gao1Rongsheng Ma2Yaqian Liu3Mingqing Liu4Fumei Zhong5Jie Hu6Shuju Li7Jihui Wu8Hualiang Jiang9Jiahai Zhang10Ke Ruan11The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China; Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, ChinaThe First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China; Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, ChinaMinistry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, ChinaMinistry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, ChinaMinistry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, ChinaMinistry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, ChinaMinistry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, ChinaMinistry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, ChinaMinistry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, ChinaThe First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China; Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, ChinaMinistry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; Corresponding author.Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; Corresponding author.Considerable developments have been observed in fragment-based lead/drug discovery (FBLD/FBDD) recently, with four drugs approved and many others under investigation. Nuclear magnetic resonance (NMR) has gained increasing popularity in FBLD due to its intrinsic capability in characterizing protein-ligand interactions in a large dynamic range of affinity, from weak hits to highly potent drugs. Here, we summarize NMR applications in fragment-based hit-to-lead evolution, including the construction of a fragment library, screening methods, spectra processing, and the delineation of the protein-ligand binding modes. These state-of-the-art NMR techniques have been exemplified in the discovery of inhibitors against multiple targets over the past five years, and they are expected to continue to provide new insights in the future.http://www.sciencedirect.com/science/article/pii/S2772516221000255Fragment-based lead/drug discoveryNMR spectroscopyProtein-ligand interactionComplex structureHit-to-lead evolution |
| spellingShingle | Lei Wang Jia Gao Rongsheng Ma Yaqian Liu Mingqing Liu Fumei Zhong Jie Hu Shuju Li Jihui Wu Hualiang Jiang Jiahai Zhang Ke Ruan Recent progress in fragment-based drug discovery facilitated by NMR spectroscopy Magnetic Resonance Letters Fragment-based lead/drug discovery NMR spectroscopy Protein-ligand interaction Complex structure Hit-to-lead evolution |
| title | Recent progress in fragment-based drug discovery facilitated by NMR spectroscopy |
| title_full | Recent progress in fragment-based drug discovery facilitated by NMR spectroscopy |
| title_fullStr | Recent progress in fragment-based drug discovery facilitated by NMR spectroscopy |
| title_full_unstemmed | Recent progress in fragment-based drug discovery facilitated by NMR spectroscopy |
| title_short | Recent progress in fragment-based drug discovery facilitated by NMR spectroscopy |
| title_sort | recent progress in fragment based drug discovery facilitated by nmr spectroscopy |
| topic | Fragment-based lead/drug discovery NMR spectroscopy Protein-ligand interaction Complex structure Hit-to-lead evolution |
| url | http://www.sciencedirect.com/science/article/pii/S2772516221000255 |
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