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Area of Science:

  • Medicinal Chemistry
  • Chemical Biology
  • Drug Discovery

Background:

  • Macrocyclic peptides are crucial for targeting therapeutically relevant proteins.
  • DNA-encoded chemical libraries (DELs) offer a powerful platform for discovering small molecule binders.
  • The integration of macrocyclic peptides with DELs has gained significant traction since 2004.

Purpose of the Study:

  • To provide a historical overview of macrocyclic peptide DEL development.
  • To review methodologies enabling the rise of macrocyclic peptide DELs.
  • To discuss the achievements and challenges in this emerging field.

Main Methods:

  • Literature review of macrocyclic peptide DELs.
  • Analysis of methods for macrocycle synthesis and encoding.
  • Examination of successful DEL screening campaigns for macrocyclic peptides.

Main Results:

  • A steady increase in the number and diversity of macrocyclic peptide DELs.
  • Identification of high-affinity and potent macrocycles against various protein targets.
  • Demonstration of DELs' substantial potential in discovering novel macrocyclic peptide therapeutics.

Conclusions:

  • Macrocyclic peptide DELs represent a rapidly advancing area in drug discovery.
  • Continued methodological innovation is key to overcoming current challenges.
  • This approach holds immense promise for developing new therapeutics.