Zinc‐triggered hydrogelation of designed β‐hairpin peptides

Peptides have been designed which undergo intramolecular folding from random coil to β‐hairpin conformation, triggered by specific environmental conditions such as temperature, pH and ionic strength. These folded, amphiphilic β‐hairpins then intermolecularly self‐assemble to form a crosslinked, fibrillar network, converting the bulk material from a free‐flowing liquid to a self‐supporting, rigid hydrogel. This work reports a new trigger: zinc‐induced hydrogelation. A pentadentate ligand with a strong propensity to chelate zinc was synthesized and coupled to the side‐chain of diaminopriopionic acid, yielding a zinc‐ligating α‐amino acid. This residue was subsequently incorporated into a 20 residue β‐hairpin peptide composed of two strand regions connected by a four residue type II’ β‐turn. Using this approach, a peptide was designed which does not fold and self‐assemble until the addition of one or more equivalents of the zinc chloride trigger. Such a responsive system is of particular interest in the development of sensor technology to detect and remediate toxic levels of zinc pollution in water or soil, as well as in the design of microfluidic devices. Funding has been supplied by the Arnold and Mabel Beckman Foundation, the HHMI Undergraduate Biological Sciences Education Program and the National Institute of Health.