Theranostics 2020; 10(22):10141-10153. doi:10.7150/thno.46985 This issue Cite

Review

The peptide PROTAC modality: a novel strategy for targeted protein ubiquitination

Jinmei Jin1*, Ye Wu1*, Jinjiao Chen1,2*, Yiwen Shen1, Lijun Zhang1, Hong Zhang1, Lili Chen1, Hebao Yuan3, Hongzhuan Chen1,4, Weidong Zhang1✉, Xin Luan1✉

1. Institute of Interdisciplinary Integrative Medicine Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
2. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
3. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109 US.
4. Department of Pharmacology and Chemical Biology, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
*These authors contribute equally to this work.

Citation:
Jin J, Wu Y, Chen J, Shen Y, Zhang L, Zhang H, Chen L, Yuan H, Chen H, Zhang W, Luan X. The peptide PROTAC modality: a novel strategy for targeted protein ubiquitination. Theranostics 2020; 10(22):10141-10153. doi:10.7150/thno.46985. https://www.thno.org/v10p10141.htm
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Abstract

Graphic abstract

Despite dramatic advances in drug discovery over the decades, effective therapeutic strategies for cancers treatment are still in urgent demands. PROteolysis TArgeting Chimera (PROTAC), a novel therapeutic modality, has been vigorously promoted in preclinical and clinical applications. Unlike small molecule PROTAC, peptide PROTAC (p-PROTAC) with advantages of high specificity and low toxicity, while avoiding the limitations of shallow binding pockets through large interacting surfaces, provides promising substitutions for E3 ubiquitin ligase complex-mediated ubiquitination of “undruggable proteins”. It is worth noting that successful applications of p-PROTAC still have some obstacles, including low stability and poor membrane permeability. Hence, we highlight that p-PROTAC combined with cell-penetrating peptides, constrained conformation technique, and targeted delivery systems could be the future efforts for potential translational research.

Keywords: peptide PROTAC, ubiquitination, undruggable proteins, E3 ligase


Citation styles

APA
Jin, J., Wu, Y., Chen, J., Shen, Y., Zhang, L., Zhang, H., Chen, L., Yuan, H., Chen, H., Zhang, W., Luan, X. (2020). The peptide PROTAC modality: a novel strategy for targeted protein ubiquitination. Theranostics, 10(22), 10141-10153. https://doi.org/10.7150/thno.46985.

ACS
Jin, J.; Wu, Y.; Chen, J.; Shen, Y.; Zhang, L.; Zhang, H.; Chen, L.; Yuan, H.; Chen, H.; Zhang, W.; Luan, X. The peptide PROTAC modality: a novel strategy for targeted protein ubiquitination. Theranostics 2020, 10 (22), 10141-10153. DOI: 10.7150/thno.46985.

NLM
Jin J, Wu Y, Chen J, Shen Y, Zhang L, Zhang H, Chen L, Yuan H, Chen H, Zhang W, Luan X. The peptide PROTAC modality: a novel strategy for targeted protein ubiquitination. Theranostics 2020; 10(22):10141-10153. doi:10.7150/thno.46985. https://www.thno.org/v10p10141.htm

CSE
Jin J, Wu Y, Chen J, Shen Y, Zhang L, Zhang H, Chen L, Yuan H, Chen H, Zhang W, Luan X. 2020. The peptide PROTAC modality: a novel strategy for targeted protein ubiquitination. Theranostics. 10(22):10141-10153.

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