Peptide-Based PROTAC: The Predator of Pathological Proteins
Open accessAbstract
Qu et al. (2020) demonstrate a peptide-induced targeted degradation of the alpha-synuclein protein, a hallmark of Parkinson's disease. Using a modular three-component design, the target-protein-specific, cell-permeable peptide disposed of alpha-synuclein via the ubiquitin-proteasome pathway rather than the standard autophagy-lysosome pathway.
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CPD-PBD-PTM is a peptide-based PROTAC targeting α-synuclein, promoting α-syn-specific degradation in SK-N-SH cells and alleviating reduced cellular activity and increased toxicity caused by α-syn overexpression.
“Qu’s team developed another peptide-based PROTAC, CPD-PBD-PTM, targeting the α-synuclein protein, which is linked to Parkinson’s syndrome. The permeable CPD-PBD-PTM peptide promotes α-syn-specific degradation in SK-N-SH cells, alleviating reduced cellular activity and increased toxicity caused by α-syn overexpression.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [533]
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Cites
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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
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Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy
Fang, Y., Wang, J., Zhao, M., Zheng, Q., Ren, C., Wang, Y., & Zhang, J. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00844 · Cited by 100 · see citing works
- Authors
- Au, Y. Z., Wang, T., Sigua, L. H., & Qi, J.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Harvard University (US)
- Corresponding author
- Qi, Jun
- Venue
- Cell Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 27
- Issue
- 6
- Pages
- 637-639
- ISSN
- 2451-9448 (ISSN-L)
- 2451-9456
- OpenAlex
- W3036113118
- Cited by
- 28
- References
- 10
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 4
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell chemical biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alex's Lemonade Stand Foundation for Childhood Cancer
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- PROTACs, alpha-synuclein, Parkinson's disease, targeted protein degradation, ubiquitin-proteasome system, autophagy-lysosome pathway, cell-permeable peptide, protein aggregation
- MeSH terms
- Autophagy, Proteasome Endopeptidase Complex, alpha-Synuclein
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