Recent Reports of Solid-Phase Cyclohexapeptide Synthesis and Applications

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Drug Development

Background:

• Macrocyclic peptides are crucial scaffolds in drug development, particularly for oncology and infectious diseases.
• Macrocyclization enhances peptide drug properties such as oral bioavailability, stability, and membrane permeability.
• Solid-phase peptide synthesis (SPPS) has advanced, enabling efficient library construction of macrocyclic peptides.

Purpose of the Study:

• To review solid-phase cyclohexapeptide synthesis methodologies published since 2013.
• To cover both on-resin and solution-phase macrocyclization techniques.
• To highlight the diverse applications of synthesized macrocyclic peptides.

Main Methods:

• Focuses on solid-phase synthesis strategies for cyclohexapeptides.
• Discusses on-resin and solution-phase macrolactamization techniques.
• Summarizes advancements in synthetic methodology and library construction.

Main Results:

• Efficient construction of macrocyclic peptide and peptidomimetic libraries is achievable.
• Macrocyclization is a key strategy for improving peptide drug-like characteristics.
• Recent synthetic advancements facilitate broader applications in drug discovery.

Conclusions:

• Solid-phase synthesis of macrocyclic peptides, particularly cyclohexapeptides, has seen significant progress.
• These methods are vital for developing orally bioavailable peptide therapeutics.
• The review underscores the utility of macrocyclic peptides in medicinal chemistry and drug development.