Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded Library
Abstract An ideal DNA‐encoded library (DEL) selection requires the library to consist of diverse core skeletons and cover chemical space as much as possible. However, the lack of efficient on‐DNA synthetic approaches toward core skeletons has greatly restricted the diversity of DEL. To mitigate this...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202307049 |
| _version_ | 1827355096409702400 |
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| author | Silin Zhang Haiman Zhang Xiawen Liu Ping Qi Tingting Tan Shengdong Wang Hui Gao Hongtao Xu Zhi Zhou Wei Yi |
| author_facet | Silin Zhang Haiman Zhang Xiawen Liu Ping Qi Tingting Tan Shengdong Wang Hui Gao Hongtao Xu Zhi Zhou Wei Yi |
| author_sort | Silin Zhang |
| collection | DOAJ |
| description | Abstract An ideal DNA‐encoded library (DEL) selection requires the library to consist of diverse core skeletons and cover chemical space as much as possible. However, the lack of efficient on‐DNA synthetic approaches toward core skeletons has greatly restricted the diversity of DEL. To mitigate this issue, this work disclosed a “Mask & Release” strategy to streamline the challenging on‐DNA core skeleton synthesis. N‐phenoxyacetamide is used as a masked phenol and versatile directing group to mediate diversified DNA‐compatible C‐H functionalization, introducing the 1st‐dimensional diversity at a defined site, and simultaneously releasing the phenol functionality, which can facilitate the introduction of the 2nd diversity. This work not only provides a set of efficient syntheses toward DNA‐conjugated drug‐like core skeletons such as ortho‐alkenyl/sulfiliminyl/cyclopropyl phenol, benzofuran, dihydrobenzofuran but also provides a paradigm for on‐DNA core skeleton synthetic method development. |
| first_indexed | 2024-03-08T04:03:29Z |
| format | Article |
| id | doaj.art-490be418e5814172b1cfb3e3096561f7 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T04:03:29Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-490be418e5814172b1cfb3e3096561f72024-02-09T08:26:35ZengWileyAdvanced Science2198-38442024-02-01116n/an/a10.1002/advs.202307049Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded LibrarySilin Zhang0Haiman Zhang1Xiawen Liu2Ping Qi3Tingting Tan4Shengdong Wang5Hui Gao6Hongtao Xu7Zhi Zhou8Wei Yi9Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology The NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Guangzhou 511436 ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology The NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Guangzhou 511436 ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology The NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Guangzhou 511436 ChinaGuangzhou Institute for Food Inspection Guangzhou 511400 ChinaShanghai Institute for Advanced Immunochemical Studies & School of Life Science and Technology ShanghaiTech University Shanghai 201210 ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology The NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Guangzhou 511436 ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology The NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Guangzhou 511436 ChinaShanghai Institute for Advanced Immunochemical Studies & School of Life Science and Technology ShanghaiTech University Shanghai 201210 ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology The NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Guangzhou 511436 ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology The NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Guangzhou 511436 ChinaAbstract An ideal DNA‐encoded library (DEL) selection requires the library to consist of diverse core skeletons and cover chemical space as much as possible. However, the lack of efficient on‐DNA synthetic approaches toward core skeletons has greatly restricted the diversity of DEL. To mitigate this issue, this work disclosed a “Mask & Release” strategy to streamline the challenging on‐DNA core skeleton synthesis. N‐phenoxyacetamide is used as a masked phenol and versatile directing group to mediate diversified DNA‐compatible C‐H functionalization, introducing the 1st‐dimensional diversity at a defined site, and simultaneously releasing the phenol functionality, which can facilitate the introduction of the 2nd diversity. This work not only provides a set of efficient syntheses toward DNA‐conjugated drug‐like core skeletons such as ortho‐alkenyl/sulfiliminyl/cyclopropyl phenol, benzofuran, dihydrobenzofuran but also provides a paradigm for on‐DNA core skeleton synthetic method development.https://doi.org/10.1002/advs.202307049benzofurandiversity‐oriented synthesisDNA‐encoded librarymask and releasesulfiliminyl phenol |
| spellingShingle | Silin Zhang Haiman Zhang Xiawen Liu Ping Qi Tingting Tan Shengdong Wang Hui Gao Hongtao Xu Zhi Zhou Wei Yi Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded Library Advanced Science benzofuran diversity‐oriented synthesis DNA‐encoded library mask and release sulfiliminyl phenol |
| title | Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded Library |
| title_full | Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded Library |
| title_fullStr | Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded Library |
| title_full_unstemmed | Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded Library |
| title_short | Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded Library |
| title_sort | mask and release strategy enabled diversity oriented synthesis for dna encoded library |
| topic | benzofuran diversity‐oriented synthesis DNA‐encoded library mask and release sulfiliminyl phenol |
| url | https://doi.org/10.1002/advs.202307049 |
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