On-Resin Synthesis of Linear Aryl Thioether Containing Peptides and in-Solution Cyclization via Cysteine SAr Reaction.

Cyclic peptides represent one of the most promising therapeutic agents in drug discovery due to their good affinity and selectivity. Herein, an on-resin synthesis of aryl thioether containing peptides and a concise cyclization strategy via chemoselective cysteine SAr reaction was developed. The arylation group could be incorporated into a series of amino acids and used for standard SPPS and peptides cyclization. Constructed cyclic peptides showed increased cellular uptakes compared to their linear peptides.