A Photo-Switchable Peptide Fibril Esterase.

Recent attempts to mimic enzyme catalysis using simple, short peptides have been successful in enhancing various reactions, but the on-demand, temporal or spatial regulation of such processes by external triggers remains a great challenge. Light irradiation is an ideal trigger for regulating molecular functionality, since it can be precisely manipulated in time and space, and because most reaction mediums do not react to light. We herein report the selection of a photo-switchable amphiphilic peptide catalyst from a small library of isomeric peptides, each containing an azobenzene-based light responsive group and a catalytic histidine residue. In its native fibrillar form, the selected peptide is efficiently and enantio-selectively active for ester hydrolysis, but after irradiation by UV light inducing trans-to-cis azobenzene isomerization, the fibrils disassemble to amorphous aggregates that are much less catalytically active. Significantly, this esterase-like activity can be manipulated multiple times, as the fibrillar peptide assembly is reversibly reduced and restored upon alternate irradiation by UV and visible light, respectively. We propose that this research may shine light on the origin of complex functions in early chemical evolution. Furthermore, it paves the way to regulate additional functions for peptide nanotechnology, such as replication, charge transfer, and delivery.