Weak affinity chromatography for evaluation of stereoisomers in early drug discovery
In early drug discovery (e.g., in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (throm...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2013
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/101288 http://hdl.handle.net/10220/16729 |
| _version_ | 1826117508520738816 |
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| author | Duong-Thi, M.-D. Bergstrom, M. Fex, T. Svensson, S. Ohlson, S. Isaksson, R. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Duong-Thi, M.-D. Bergstrom, M. Fex, T. Svensson, S. Ohlson, S. Isaksson, R. |
| author_sort | Duong-Thi, M.-D. |
| collection | NTU |
| description | In early drug discovery (e.g., in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (thrombin) using weak affinity chromatography–mass spectrometry (WAC-MS). Affinity determinations by WAC showed that minor changes in stereoisomeric configuration could have a major impact on affinity. The ability of WAC-MS to provide instant information about stereoselectivity and binding affinities directly from analyte mixtures is a great advantage in fragment library screening and drug lead development. |
| first_indexed | 2024-10-01T04:28:44Z |
| format | Journal Article |
| id | ntu-10356/101288 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:28:44Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/1012882020-03-07T12:18:15Z Weak affinity chromatography for evaluation of stereoisomers in early drug discovery Duong-Thi, M.-D. Bergstrom, M. Fex, T. Svensson, S. Ohlson, S. Isaksson, R. School of Biological Sciences DRNTU::Science::Biological sciences::Microbiology In early drug discovery (e.g., in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (thrombin) using weak affinity chromatography–mass spectrometry (WAC-MS). Affinity determinations by WAC showed that minor changes in stereoisomeric configuration could have a major impact on affinity. The ability of WAC-MS to provide instant information about stereoselectivity and binding affinities directly from analyte mixtures is a great advantage in fragment library screening and drug lead development. 2013-10-23T07:07:27Z 2019-12-06T20:36:08Z 2013-10-23T07:07:27Z 2019-12-06T20:36:08Z 2013 2013 Journal Article Duong-Thi, M.-D., Bergstrӧm, M., Fex, T., Svensson, S., Ohlson, S., & Isaksson, R. (2013). Weak affinity chromatography for evaluation of stereoisomers in early drug discovery. Journal of biomolecular screening, 18(6), 748-755. https://hdl.handle.net/10356/101288 http://hdl.handle.net/10220/16729 10.1177/1087057113480391 en Journal of biomolecular screening |
| spellingShingle | DRNTU::Science::Biological sciences::Microbiology Duong-Thi, M.-D. Bergstrom, M. Fex, T. Svensson, S. Ohlson, S. Isaksson, R. Weak affinity chromatography for evaluation of stereoisomers in early drug discovery |
| title | Weak affinity chromatography for evaluation of stereoisomers in early drug discovery |
| title_full | Weak affinity chromatography for evaluation of stereoisomers in early drug discovery |
| title_fullStr | Weak affinity chromatography for evaluation of stereoisomers in early drug discovery |
| title_full_unstemmed | Weak affinity chromatography for evaluation of stereoisomers in early drug discovery |
| title_short | Weak affinity chromatography for evaluation of stereoisomers in early drug discovery |
| title_sort | weak affinity chromatography for evaluation of stereoisomers in early drug discovery |
| topic | DRNTU::Science::Biological sciences::Microbiology |
| url | https://hdl.handle.net/10356/101288 http://hdl.handle.net/10220/16729 |
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