Fluoroalkylation promotes cytosolic peptide delivery

Cytosolic delivery of peptides remains a challenging task owing to their susceptibility to enzymatic degradation and the existence of multiple intracellular barriers. Here, we report a new strategy to address these issues by decoration of a fluorous tag on the terminal of cargo peptides. The fluorous-tagged peptides were assembled into nanostructures, efficiently internalized by cells via several endocytic pathways and released into the cytosol after endosomal escape. They were relatively stable against enzymatic degradation and showed much higher efficiency than nonfluorinated analogs and cell penetrant peptide–conjugated ones. The proposed strategy also efficiently delivered a proapoptotic peptide into specific sites in the cells and restored the function of cargo peptide after cytosolic delivery. The fluorous-tagged proapoptotic peptide efficiently inhibited tumor growth in vivo. This study provides an efficient fluorination strategy to promote the cytosolic delivery of peptides.

Fluorous-tag assisted synthesis of bile acid–bisphosphonate conjugates via orthogonal click reactions: an access to potential anti-resorption bone drugs

Click reactions and fluorous separations afford bile acid–bisphosphonate conjugates.

Highly efficient one-pot multienzyme (OPME) synthesis of glycans with fluorous-tag assisted purification

Fluorous-tagged glycans with an oligo(ethylene glycol) linker are well tolerated glycosyltransferase substrates for high-yield OPME synthesis and facile FSPE purification of glycans.