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Published on: August 15, 2016
Tyrosine-Selective Polyfluoroaryl Modification Enables Bioactive Peptides with Enhanced Membrane Permeability and
Quan Zuo1,2, Guoqing Li3, Quanshu He1,2
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
None:
We report a tyrosine-selective polyfluoroaryl modification strategy using tetrafluoro-substituted N-methyl luminol reagents. Under mild oxidative conditions, this platform achieves rapid and chemoselective functionalization of Tyr residues across diverse bioactive peptides. The installed tetrafluoroaryl motif serves as a versatile handle for linker-free peptide-peptide ligation via SNAr with N-terminal cysteines, as confirmed by 19F NMR and X-ray crystallography. Furthermore, this modification significantly enhances the membrane permeability of cell-penetrating peptides, enabling the cytosolic delivery of macromolecular cargos. This work provides a unified workflow for peptide fluorination, programmable ligation, and physicochemical optimization.
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