Late-Stage Functionalization of Peptides on the Solid Phase.

Area of Science:

• Medicinal Chemistry
• Organic Chemistry
• Biotechnology

Background:

• Peptide modification is crucial for tailoring structure and function, especially in peptide drug development.
• Developing methods for incorporating non-canonical residues into peptides is highly sought after.
• On-resin late-stage functionalization provides a cost- and time-efficient approach for peptide modification.

Purpose of the Study:

• To provide an overview of chemical approaches for on-resin late-stage peptide functionalization.
• To highlight recent advancements in the field, particularly those developed in the past decade.
• To showcase the potential of these methods in streamlining peptide therapeutics development.

Main Methods:

• Review of various chemical strategies including nucleophilic substitution, carbonyl chemistry, metal catalysis, and photocatalysis.
• Discussion of methods compatible with both short and long peptides.
• Examination of applications in high-throughput peptide library synthesis.

Main Results:

• Numerous chemical approaches for on-resin late-stage peptide functionalization have been developed.
• These methods are effective for modifying peptides and modulating their bioactivity.
• Successful synthesis of peptide libraries in high-throughput formats has been demonstrated.

Conclusions:

• On-resin late-stage peptide functionalization is a powerful tool for peptide drug development.
• The reviewed chemical methods offer efficiency and versatility for peptide modification.
• These techniques hold significant promise for the future of peptide therapeutics.