Solid-Phase Peptide Modification via Deaminative Photochemical Csp³ -Csp³ Bond Formation Using Katritzky Salts

Area of Science:

• Chemical Biology
• Organic Synthesis
• Peptide Chemistry

Background:

• Unnatural amino acids enhance peptide binding affinity and stability.
• Synthesizing unnatural amino acids is complex and time-consuming.
• Limited commercial availability of specialized amino acids hinders peptide research.

Purpose of the Study:

• To develop a streamlined method for late-stage peptide modification.
• To enable rapid diversification of peptides without de novo amino acid synthesis.
• To demonstrate a novel deaminative functionalization strategy at lysine residues.

Main Methods:

• Peptide functionalization directly on solid-support.
• Conversion of lysine residues to Katritzky salts.
• Photochemical Giese reaction under mild conditions.

Main Results:

• A two-step protocol for peptide functionalization was established.
• The method is compatible with diverse substrates, lysine analogues, resins, and proteinogenic amino acids.
• Successful functionalization of peptides up to 15 amino acids was achieved.

Conclusions:

• This method offers a late-stage modification route for rapid peptide diversification.
• It circumvents the need for laborious amino acid synthesis.
• The protocol facilitates the functionalization of longer, biologically relevant peptides.