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Related Experiment Video

Updated: Aug 12, 2025

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
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Peptide-based PROTACs: Current Challenges and Future Perspectives.

Huidan Wang1, Miao Chen1, Xiaoyuan Zhang1

  • 1School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255000, China.

Current Medicinal Chemistry
|January 31, 2023
PubMed
Summary
This summary is machine-generated.

Peptide-based PROTACs offer a new way to degrade challenging proteins. This review explores their design, applications, and challenges for clinical use.

Keywords:
E3 ubiquitinPeptide-based PROTACdrug deliverymutant proteinstargeted protein degradationundruggable protein

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Proteolysis-targeting chimeras (PROTACs) are emerging therapeutics for undruggable or resistant proteins.
  • Small molecule PROTACs face limitations due to the scarcity of suitable warheads for protein recruitment.
  • Advances in structural biology and computational prediction facilitate the design of selective peptides for PROTACs.

Purpose of the Study:

  • To review recent advancements in peptide-based PROTACs.
  • To discuss practical methods for identifying peptide PROTAC candidates.
  • To highlight challenges and propose solutions for clinical translation of peptide PROTACs.

Main Methods:

  • Literature review of recent progress in peptide-based PROTAC design and application.
  • Analysis of practical approaches for obtaining candidate peptides.
  • Discussion of hurdles in delivery and bioavailability for clinical development.

Main Results:

  • Peptide-based PROTACs are increasingly feasible for targeting previously undruggable proteins.
  • New strategies are emerging for designing and identifying suitable peptides for PROTACs.
  • Significant challenges remain in peptide PROTAC delivery and bioavailability.

Conclusions:

  • Peptide-based PROTACs represent a promising therapeutic strategy for challenging protein targets.
  • Further research is needed to overcome delivery and bioavailability issues for clinical application.
  • Accelerating the clinical development of peptide PROTACs requires collaborative efforts to address current limitations.