Directional assembly of stapled α‑helical peptide

De novo design of stapled peptide-based self-assembly attracts vast interests yet still challenging. The development of an oxidation trigger for peptide stapling and subsequent self-assembly is described here. A self-assembling sequence, Fmoc-R(RCEX)2-NH2, transformed from random coil to -helical structure upon disulphide bonding of the flanking cysteine residues positioning at i/i+4 locations. The stapling form of this peptide enforces a conformational restraint that affords driving force for the self-assembly into nanorod/nanovesicle structures. Moreover, we demonstrated that these assembling materials can transport siRNA into cancer cells and immediately release the cargo in a reductive environment.