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.