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There are numerous evaluations of natural products, of which majority are food bioactives, performed up to date for their various health beneficial activities via targeting specific proteins. However, the direct identification of a targeted protein remains unexplored for natural occurring compounds. Proteolysis targeting chimera (PROTAC) is a type of bifunctional chimeric molecules that can directly degrade the binding proteins targeted by bioactive molecules in an ubiquitin-proteasome pathway. As the agents in protein degradation dependent on ubiquitin ligase, the bifunctional molecule connects the target protein ligand and E3 ligase ligand together via an appropriate linker. It is highly selective and efficient to induce the ubiquitin-mediated degradation of targeted binding proteins. Therefore, it has been demonstrated that the PROTAC technology has broad application in the modulation of the target protein level. In this review, we outlined the advances in PROTAC combined molecule compounds, summarized its quantitative structure-activity relationship, and finally reviewed the methods applied in identifying the target proteins of natural products. We hope it will provide an insightful application of PROTAC techniques in the target protein identification of natural products including food bioactive molecules.


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Potential application of proteolysis targeting chimera (PROTAC) modification technology in natural products for their targeted protein degradation

Show Author's information Guliang YangaHaiyan ZhongaXinxin XiaaZhiwen Qib( )Chengzhang WangbShiming Lic( )
National Engineering Laboratory for Rice and By-products Processing, Food Science and Engineering College, Central South University of Forestry and Technology, Changsha 410004, China
Institute of Chemical Industry of Forest Products, CAF, Nanjing 210042, China
Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Huanggang Normal University, Huanggang 438000, China

Peer review under responsibility of KeAi Communications Co., Ltd.

Abstract

There are numerous evaluations of natural products, of which majority are food bioactives, performed up to date for their various health beneficial activities via targeting specific proteins. However, the direct identification of a targeted protein remains unexplored for natural occurring compounds. Proteolysis targeting chimera (PROTAC) is a type of bifunctional chimeric molecules that can directly degrade the binding proteins targeted by bioactive molecules in an ubiquitin-proteasome pathway. As the agents in protein degradation dependent on ubiquitin ligase, the bifunctional molecule connects the target protein ligand and E3 ligase ligand together via an appropriate linker. It is highly selective and efficient to induce the ubiquitin-mediated degradation of targeted binding proteins. Therefore, it has been demonstrated that the PROTAC technology has broad application in the modulation of the target protein level. In this review, we outlined the advances in PROTAC combined molecule compounds, summarized its quantitative structure-activity relationship, and finally reviewed the methods applied in identifying the target proteins of natural products. We hope it will provide an insightful application of PROTAC techniques in the target protein identification of natural products including food bioactive molecules.

Keywords: Ligand, Natural products, PROTAC, Target binding

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Received: 02 October 2021
Revised: 29 October 2021
Accepted: 29 October 2021
Published: 25 November 2021
Issue date: March 2022

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© 2022 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

Acknowledgements

This research work was supported by the key scientific research projects of Hunan Provincial Department of Education of China (No. 19A513), the National Nonprofit Institute Research Grant of CAFINT, China (No. CAFYBB2018GA001) and Grant from Hubei Province, China (GRANT number 2019ABA100).

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