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

Abstract

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.

Self-Assembling Peptide Dendron Nanoparticles with High Stability and a Multimodal Antimicrobial Mechanism of Action

“…Circular dichroism (CD) spectroscopy is commonly used to determine the secondary structure of peptides. As shown in Figures i and S6, the CD investigation of these peptide dendrons revealed a negative maximum at approximately 200 nm and a weak maximum in the range of 220–230 nm in PB solution, indicating a polyproline II helical structure arrangement . Additionally, these peptide dendrons retained their polyproline II helical structure conformation in small unilamellar vesicle (SUV, 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphoethanolamine/1-palmitoyl-2-oleoyl- sn -glycero-3-phosphoglycerol (POPE/POPG) = 3:1) suspensions, which have a prokaryotic membrane-comparable hydrophobic and negative-charged environment.…”

“…As shown in Figures 1i and S6, the CD investigation of these peptide dendrons revealed a negative maximum at approximately 200 nm and a weak maximum in the range of 220−230 nm in PB solution, indicating a polyproline II helical structure arrangement. 41 Additionally, these peptide dendrons retained their polyproline II helical structure conformation in small unilamellar vesicle (SUV, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPE/POPG) = 3:1) suspensions, which have a prokaryotic membrane-comparable hydrophobic and negativecharged environment. As the incubation environment changed from PB to membrane-mimetic environments, the peptide dendrons did not convert from their disordered conformation into helical or β-sheet structures (becomes amphipathic), as occurs for traditional AMPs (such as cecropins, magainins, and defensins).…”

Peptide-Based Supramolecular Systems Chemistry

“…While the tripeptide GPO dissolves in water, Fmoc-GPO was found to readily crystallize into a lefthanded helix, resembling a polyproline II architecture as seen in single collagen helices. 72 X-ray analysis of the crystal structure seems to suggest that the interactions governing interhelix interactions are still present in Fmoc-GPO. Uniquely, Fmoc-FF coassembled with Fmoc-GPO forms a hydrogel where the dominant structure appears to be a polyproline II-type helix rather than the β-stacked structure commonly found in FF-based assemblies.…”

Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin

“…Hydrogels and nanogels can be prepared using synthetic [26][27][28] or natural polymers [29][30][31][32] or peptide sequences. 33,34 With respect to polymers, peptides exhibit several advantages such as high biocompatibility, biodegradability and tunability. Fmoc-FF (N αfluorenylmethyloxycarbonyl diphenylalanine) hydrogelator ( Figure 1) represents one of the most studied peptide sequences for hydrogels formulation, thanks to its capability to gelificate under physiological conditions, required for biomedical applications.…”