Peptide Boronic Acids by Late-Stage Hydroboration on the Solid Phase

Area of Science:

• Organic Chemistry
• Biochemistry
• Medicinal Chemistry

Background:

• Organoboron compounds are valuable in diverse research areas.
• Incorporating boronic acids into biomolecules is a significant synthetic challenge.
• Existing methods for peptide boronic acid synthesis have limitations.

Purpose of the Study:

• To develop efficient on-resin chemical syntheses for peptide boronic acids.
• To create methods for incorporating aliphatic and vinylogous peptide boronic acids into peptides and peptoids.
• To explore the applications of these novel peptide boronic acids.

Main Methods:

• Transition metal-catalyzed late-stage hydroboration of alkene and alkyne groups in peptides and peptoids.
• On-resin synthesis utilizing allyl- and propargylglycine residues.
• Derivatization via the Petasis reaction and carbohydrate binding studies.

Main Results:

• Successful synthesis of peptide boronic acids with shorter linkers compared to previous methods.
• Methods demonstrated regio- and stereoselectivity, compatibility with canonical amino acids, and applicability to various peptide sequences.
• Demonstrated reversible carbohydrate binding capabilities of the synthesized peptide boronic acids.

Conclusions:

• The developed methods provide efficient access to peptide boronic acids.
• These compounds show promise for drug discovery, glycan-specific recognition, controlled release, and diagnostics.
• The synthesis is versatile and applicable to complex peptide sequences.