A Redox-Sensitive Resin Linker for the Solid Phase Synthesis of C-Terminal Modified Peptides

With the rapid development of combinatorial chemistry using solid phase synthesis, there is a great deal of interest in developing new solid phase linkers, which are stable during the solid phase synthesis process and yet readily cleavable under mild conditions. By taking advantage of a “trimethyl lock”-facilitated lactonization reaction, we have developed a redox-sensitive resin linker for the synthesis of C-terminal-modified peptides. The cleavage only requires mild reducing agents such as sodium hydrosulfite, which is not expected to cause any problem with the commonly seen organic functional groups. Using this new linker, three short peptides were synthesized with high isolated yields (70−90%). Such a linker could potentially be used for the synthesis of modified peptide libraries, which allows for the ready cleavage of the linker under mild conditions.