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

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...

Full description

Saved in:
Bibliographic Details
Published in:Theranostics 2020-01, Vol.10 (22), p.10141-10153
Main Authors: Jin, Jinmei, Wu, Ye, Chen, Jinjiao, Shen, Yiwen, Zhang, Lijun, Zhang, Hong, Chen, Lili, Yuan, Hebao, Chen, Hongzhuan, Zhang, Weidong, Luan, Xin
Format: Article
Language:English
Subjects:
Animals
Clinical trials
Drug Delivery Systems - methods
Drug resistance
Enzymes
Estrogens
Humans
Kinases
Ligands
Medical research
Mutation
Peptides
Peptides - metabolism
Permeability
Proteins
Proteins - metabolism
Proteolysis
Review
Ubiquitin-Protein Ligases - metabolism
Ubiquitination - drug effects
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.46985