Recent advances in peptide macrocyclization strategies.

Area of Science:

• * Peptide chemistry and supramolecular chemistry.
• * Organic synthesis and materials science.

Background:

• * Peptide-based macrocycles exhibit unique spatial structures, driving interest in diverse research areas.
• * Applications span from potent antibiotics against resistant strains to advanced functional biomaterials.
• * Traditional monocyclic peptides are complemented by emerging polycyclic, spherical, and cylindrical systems.

Purpose of the Study:

• * To review and discuss state-of-the-art macrocyclization methodologies for peptides and peptidomimetics.
• * To provide insights into the practical advantages and limitations of these techniques.
• * To discuss synthetic-technical aspects, challenges, and future outlook in the field.

Main Methods:

• * Chemical strategies: Native chemical ligation, transition metal catalysis.
• * Biological strategies: Post-translational enzymatic modification, genetic code reprogramming.
• * Supramolecular strategies: Mechanically interlocked systems, metal-directed folding, noncovalent self-assembly.

Main Results:

• * A comprehensive survey of diverse macrocyclization techniques for peptides and peptidomimetics.
• * Analysis of the strengths and weaknesses of various synthetic approaches.
• * Identification of key breakthroughs enabling complex cyclic peptide architectures.

Conclusions:

• * Significant progress has been made in peptide macrocyclization strategies.
• * The field presents opportunities for developing novel therapeutics and materials.
• * Further research is needed to address current challenges and unlock full potential.