Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins
Membrane proteins constitute the largest class of drug targets but they present many challenges in drug discovery. Importantly, the discovery of potential drug candidates is hampered by the limited availability of efficient methods for screening drug-protein interactions. In this work we present a n...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2016
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/80267 http://hdl.handle.net/10220/40453 |
| _version_ | 1811680878771830784 |
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| author | Duong-Thi, Minh-Dao Bergström, Maria Edwards, Katarina Eriksson, Jonny Ohlson, Sten To Yiu Ying, Janet Torres, Jaume Agmo Hernández, Víctor |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Duong-Thi, Minh-Dao Bergström, Maria Edwards, Katarina Eriksson, Jonny Ohlson, Sten To Yiu Ying, Janet Torres, Jaume Agmo Hernández, Víctor |
| author_sort | Duong-Thi, Minh-Dao |
| collection | NTU |
| description | Membrane proteins constitute the largest class of drug targets but they present many challenges in drug discovery. Importantly, the discovery of potential drug candidates is hampered by the limited availability of efficient methods for screening drug-protein interactions. In this work we present a novel strategy for rapid identification of molecules capable of binding to a selected membrane protein. An integral membrane protein (human aquaporin-1) was incorporated into planar lipid bilayer disks (lipodisks), which were subsequently covalently coupled to porous derivatized silica and packed into HPLC columns. The obtained affinity columns were used in a typical protocol for fragment screening by weak affinity chromatography (WAC), in which one hit was identified out of a 200 compound collection. The lipodisk-based strategy, which ensures a stable and native-like lipid environment for the protein, is expected to work also with other membrane proteins and screening procedures. |
| first_indexed | 2024-10-01T03:32:03Z |
| format | Journal Article |
| id | ntu-10356/80267 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:32:03Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/802672023-02-28T16:58:02Z Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins Duong-Thi, Minh-Dao Bergström, Maria Edwards, Katarina Eriksson, Jonny Ohlson, Sten To Yiu Ying, Janet Torres, Jaume Agmo Hernández, Víctor School of Biological Sciences Biological Sciences Membrane proteins constitute the largest class of drug targets but they present many challenges in drug discovery. Importantly, the discovery of potential drug candidates is hampered by the limited availability of efficient methods for screening drug-protein interactions. In this work we present a novel strategy for rapid identification of molecules capable of binding to a selected membrane protein. An integral membrane protein (human aquaporin-1) was incorporated into planar lipid bilayer disks (lipodisks), which were subsequently covalently coupled to porous derivatized silica and packed into HPLC columns. The obtained affinity columns were used in a typical protocol for fragment screening by weak affinity chromatography (WAC), in which one hit was identified out of a 200 compound collection. The lipodisk-based strategy, which ensures a stable and native-like lipid environment for the protein, is expected to work also with other membrane proteins and screening procedures. NRF (Natl Research Foundation, S’pore) Accepted version 2016-04-15T06:48:51Z 2019-12-06T13:46:12Z 2016-04-15T06:48:51Z 2019-12-06T13:46:12Z 2016 Journal Article Duong-Thi, M. D., Bergström, M., Edwards, K., Eriksson, J., Ohlson, S., To Yiu Ying, J., et al. (2016). Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins. Analyst, 141(3), 981-988. 0003-2654 https://hdl.handle.net/10356/80267 http://hdl.handle.net/10220/40453 10.1039/C5AN02105G en The Analyst 22 p. application/pdf application/pdf |
| spellingShingle | Biological Sciences Duong-Thi, Minh-Dao Bergström, Maria Edwards, Katarina Eriksson, Jonny Ohlson, Sten To Yiu Ying, Janet Torres, Jaume Agmo Hernández, Víctor Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins |
| title | Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins |
| title_full | Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins |
| title_fullStr | Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins |
| title_full_unstemmed | Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins |
| title_short | Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins |
| title_sort | lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins |
| topic | Biological Sciences |
| url | https://hdl.handle.net/10356/80267 http://hdl.handle.net/10220/40453 |
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