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Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
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Biocompatible strategies for peptide macrocyclisation.

Junming He1, Pritha Ghosh1, Christoph Nitsche1

  • 1Research School of Chemistry, Australian National University Canberra ACT Australia christoph.nitsche@anu.edu.au.

Chemical Science
|February 16, 2024
PubMed
Summary

Peptide macrocyclisation enhances drug properties like stability and cell uptake. This perspective explores biocompatible reactions for peptide drug development, distinguishing them from bioorthogonal methods.

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Area of Science:

  • Medicinal Chemistry
  • Biochemistry
  • Drug Discovery

Background:

  • Peptides are promising drug candidates but face bioavailability and stability challenges.
  • Macrocyclisation is a key modification to improve peptide drug properties.
  • Biocompatible peptide macrocyclisation is increasingly important for drug screening.

Purpose of the Study:

  • To differentiate biocompatible from bioorthogonal peptide macrocyclisation conditions.
  • To present key strategies for biocompatible peptide macrocyclisation.
  • To contextualise these strategies within modern peptide screening methods.

Main Methods:

  • Review of existing literature on peptide macrocyclisation.
  • Analysis of biocompatible and bioorthogonal reaction conditions.
  • Categorisation of macrocyclisation strategies.

Main Results:

  • Macrocyclisation significantly enhances peptide affinity, selectivity, stability, and permeability.
  • Biocompatible conditions are crucial for integrating macrocyclisation with screening.
  • Several biocompatible macrocyclisation strategies are available for peptide modification.

Conclusions:

  • Biocompatible peptide macrocyclisation is essential for overcoming drug development hurdles.
  • This approach enables efficient screening and development of peptide-based therapeutics.
  • The review provides a valuable overview of current biocompatible macrocyclisation techniques.