Natural Occurring and Engineered Enzymes for Peptide Ligation and Cyclization

Area of Science:

• Biochemistry
• Chemical Biology
• Medicinal Chemistry

Background:

• Peptides are gaining prominence as therapeutic agents.
• Novel chemical and enzymatic strategies are crucial for peptide synthesis and modification.
• Enzymes offer high regio- and chemoselectivity for peptide ligation.

Purpose of the Study:

• To review natural and engineered peptide ligases for therapeutic applications.
• To summarize the advantages and disadvantages of various enzyme classes.
• To highlight recent advancements in enzymatic peptide ligation and cyclization.

Main Methods:

• Focus on enzyme classes including Sortases, Asparaginyl Endoproteases, Trypsin-related enzymes, and subtilisin-derived variants.
• Review of literature on enzymatic peptide bond formation.
• Analysis of recent developments in peptide ligation and cyclization strategies.

Main Results:

• Peptide ligases are effective tools for forming new peptide (amide) bonds.
• Sortases, Asparaginyl Endoproteases, Trypsin-related enzymes, and subtilisin variants show distinct properties for peptide synthesis.
• Recent developments enable efficient peptide ligation and cyclization using engineered enzymes.

Conclusions:

• Enzymatic peptide ligation is a powerful approach for developing peptide therapeutics.
• Engineered peptide ligases, particularly subtilisin variants, offer significant advantages.
• Further advancements in enzyme engineering will accelerate peptide drug development.