Cover Image, Volume 108, Issue 5

Multi enzyme‐responsive peptide systems have the potential to provide greater target selectivity than many single responsive systems, and a means for indirect enzyme detection. Maynard et al . report dual enzyme‐responsive peptides that require sequential digestion by two enzymes for cargo release. The peptides are synthesized by coupling chymotrypsin, papain or caspase 3 substrates to the ɛ‐amine of lysine. Enzymatic cleavage of these substrates unmasks the ɛ‐amine, allowing for digestion by a second enzyme, trypsin, which can be monitored colorimetrically. In the presence of only a single enzyme, no colorimetric signal is observed, demonstrating that both enzymes must be present for release. (doi: 10.1002/bip.23035 )