Tyrosine-Selective Polyfluoroaryl Modification Enables Bioactive Peptides with Enhanced Membrane Permeability and...

Area of Science:

• Chemical Biology
• Organic Chemistry
• Biochemistry

Background:

• Peptide modification is crucial for developing new therapeutics.
• Existing methods for peptide functionalization and ligation can be complex and inefficient.

Purpose of the Study:

• To develop a tyrosine-selective modification strategy for peptides.
• To enable linker-free peptide ligation and enhance peptide physicochemical properties.

Main Methods:

• Utilized tetrafluoro-substituted N-methyl luminol reagents for tyrosine modification.
• Employed mild oxidative conditions for chemoselective functionalization.
• Confirmed peptide ligation using 19F NMR and X-ray crystallography.

Main Results:

• Achieved rapid and selective functionalization of tyrosine residues in diverse peptides.
• Demonstrated successful linker-free peptide-peptide ligation via S_NAr reactions.
• Showcased enhanced membrane permeability and cytosolic delivery of peptides.

Conclusions:

• Developed a versatile platform for peptide fluorination and ligation.
• The strategy facilitates programmable peptide assembly and optimization of biological properties.
• This workflow offers a unified approach for advanced peptide engineering.