Controlling the assembly and disassembly of cross‐β‐sheet‐forming peptides is one of the predominant challenges for this class of supramolecular material. As they constitute a continuously propagating material, every atomic change can be exploited to bring about distinct responses at the architectural level. We report herein that, by using rational chemical design, serine and methionine can both be used as orthogonal chemical triggers to signal assembly/disassembly through their corresponding stimuli. Serine is used to construct an ester‐bond oligopeptide that can undergo O,N‐acyl rearrangement, whereas methionine is sensitive to oxidation by H2O2. Using the example peptide sequence, KIKISQINM, we demonstrate that assembly and disassembly can be independently controlled on demand.

The assembly and disassembly of the oligopeptide KIKISQINM is independently controlled by two different external stimuli. The assembly process involves the kosmotrope‐induced hydrolysis of a phenylboronic acid–carbamate cage followed by an intramolecular O,N‐acyl shift to release a fibrilizing oligopeptide. On demand, the cross‐β‐sheet structure can be disassembled by oxidation of the thioether residues (methionine) in the presence of hydrogen peroxide. This work broadens the chemical tools and design concepts for controlling the supramolecular organization of self‐assembling peptides. More information can be found in the communication by T. Weil, D. Y. W. Ng, et al. on page 1376 in Issue 11, 2019 (DOI: 10.1002/cbic.201800781).