Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor
Flap structure-specific endonuclease 1 (FEN1) is one of the enzymes that involve in Eukaryotic DNA replication and repair. Recent studies have proved that FEN1 is highly over-expressed in various types of cancer cells and is a drug target. However, a limited number of FEN1 inhibitors has been identi...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2017
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| Online Access: | https://hdl.handle.net/10356/85086 http://hdl.handle.net/10220/43624 |
| _version_ | 1826122264952700928 |
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| author | Wu, Haixia Ye, Ruijuan Huang, Dejian Li, Tianhu Ba, Sai Zhang, Hao Lee, Jasmine Yiqin |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Wu, Haixia Ye, Ruijuan Huang, Dejian Li, Tianhu Ba, Sai Zhang, Hao Lee, Jasmine Yiqin |
| author_sort | Wu, Haixia |
| collection | NTU |
| description | Flap structure-specific endonuclease 1 (FEN1) is one of the enzymes that involve in Eukaryotic DNA replication and repair. Recent studies have proved that FEN1 is highly over-expressed in various types of cancer cells and is a drug target. However, a limited number of FEN1 inhibitors has been identified and approved. Herein, we investigate the catalytic activity of FEN1, and propose a substrate-based inhibitor. As a consequence, one of the phosphorothioate-modified substrates is proved to exhibit the most efficient inhibitory effect in our in vitro examinations. A novelly-designed substrate-based FEN1 inhibitor was accordingly constructed and determined a remarkable IC50 value. |
| first_indexed | 2024-10-01T05:45:39Z |
| format | Journal Article |
| id | ntu-10356/85086 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:45:39Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/850862023-02-28T19:22:28Z Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor Wu, Haixia Ye, Ruijuan Huang, Dejian Li, Tianhu Ba, Sai Zhang, Hao Lee, Jasmine Yiqin School of Physical and Mathematical Sciences FEN1 Phosphorothioate Flap structure-specific endonuclease 1 (FEN1) is one of the enzymes that involve in Eukaryotic DNA replication and repair. Recent studies have proved that FEN1 is highly over-expressed in various types of cancer cells and is a drug target. However, a limited number of FEN1 inhibitors has been identified and approved. Herein, we investigate the catalytic activity of FEN1, and propose a substrate-based inhibitor. As a consequence, one of the phosphorothioate-modified substrates is proved to exhibit the most efficient inhibitory effect in our in vitro examinations. A novelly-designed substrate-based FEN1 inhibitor was accordingly constructed and determined a remarkable IC50 value. MOE (Min. of Education, S’pore) Accepted version 2017-08-22T04:02:07Z 2019-12-06T15:56:46Z 2017-08-22T04:02:07Z 2019-12-06T15:56:46Z 2016 Journal Article Ba, S., Zhang, H., Lee, J. Y., Wu, H., Ye, R., Huang, D., et al. (2016). Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor. Bioorganic & Medicinal Chemistry, 24(9), 1988-1992. 0968-0896 https://hdl.handle.net/10356/85086 http://hdl.handle.net/10220/43624 10.1016/j.bmc.2016.03.025 en Bioorganic & Medicinal Chemistry © 2016 Elsevier. This is the author created version of a work that has been peer reviewed and accepted for publication by Bioorganic & Medicinal Chemistry, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.bmc.2016.03.025]. 6 p. application/pdf |
| spellingShingle | FEN1 Phosphorothioate Wu, Haixia Ye, Ruijuan Huang, Dejian Li, Tianhu Ba, Sai Zhang, Hao Lee, Jasmine Yiqin Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor |
| title | Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor |
| title_full | Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor |
| title_fullStr | Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor |
| title_full_unstemmed | Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor |
| title_short | Investigation of human flap structure-specific endonuclease 1 (FEN1) activity on primer-template models and exploration of a substrate-based FEN1 inhibitor |
| title_sort | investigation of human flap structure specific endonuclease 1 fen1 activity on primer template models and exploration of a substrate based fen1 inhibitor |
| topic | FEN1 Phosphorothioate |
| url | https://hdl.handle.net/10356/85086 http://hdl.handle.net/10220/43624 |
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