Collagen-Inspired Helical Peptide Coassembly Forms a Rigid Hydrogel with Twisted Polyproline II Architecture.

Collagen, the most abundant protein in mammals, possesses notable cohesion and elasticity properties and efficiently induces tissue regeneration. The Gly-Pro-Hyp canonical tripeptide repeating unit of the collagen superhelix has been well-characterized. However, to date, the shortest tripeptide repeat demonstrated to attain a helical conformation contained 3-10 peptide repeats. Here, taking a minimalistic approach, we studied a single repeating unit of collagen in its protected form, Fmoc-Gly-Pro-Hyp. The peptide formed single crystals displaying left-handed polyproline II superhelical packing, as in the native collagen single strand. The crystalline assemblies also display head-to-tail H-bond interactions and an "aromatic zipper" arrangement at the molecular interface. The coassembly of this tripeptide, with Fmoc-Phe-Phe, a well-studied dipeptide hydrogelator, produced twisted helical fibrils with a polyproline II conformation and improved hydrogel mechanical rigidity. The design of these peptides illustrates the possibility to assemble superhelical nanostructures from minimal collagen-inspired peptides with their potential use as functional motifs to introduce a polyproline II conformation into hybrid hydrogel assemblies.