Hydrogelation and Self-Assembly of Fmoc-Tripeptides: Unexpected Influence of Sequence on Self-Assembled Fibril Structure, and Hydrogel Modulus and Anisotropy

Abstract

The self-assembly and hydrogelation properties of two Fmoc-tripeptides [Fmoc = N-(fluorenyl-9-methoxycarbonyl)] are investigated, in borate buffer and other basic solutions. A remarkable difference in self-assembly properties is observed comparing Fmoc-VLK(Boc) with Fmoc-K(Boc)LV, both containing K protected by N(epsilon)-tert-butyloxycarbonate (Boc). In borate buffer, the former peptide forms highly anisotropic fibrils which show local alignment, and the hydrogels show flow-aligning properties. In contrast, Fmoc-K(Boc)LV forms highly branched fibrils that produce isotropic hydrogels with a much higher modulus (G' > 10(4) Pa), and lower concentration for hydrogel formation. The distinct self-assembled structures are ascribed to conformational differences, as revealed by secondary structure probes (CD, FTIR, Raman spectroscopy) and X-ray diffraction. Fmoc-VLK(Boc) forms well-defined beta-sheets with a cross-beta X-ray diffraction pattern, whereas Fmoc-KLV(Boc) forms unoriented assemblies with multiple stacked sheets. Interchange of the K and V residues when inverting the tripeptide sequence thus leads to substantial differences in self-assembled structures, suggesting a promising approach to control hydrogel properties.

Biocatalytic Self-Assembly of Tripeptide Gels and Emulsions

“…However, there is an upturn in GÕ and GÕÕ moduli at higher frequencies ( Figure S11), which is possibly explained by a thickening instability, as previously mentioned. [39][40] The highest elasticity would be expected for the sample with the highest level of entanglement of fibers ( Figure 3E), as observed for an enzyme-triggered self-assembly of octapeptides. 41 Even though the error bars for the 3.3 μM alkaline phosphatase sample are larger than for the other enzyme concentration used, which suggests higher variability in the properties of this material, it presents the highest GÕ and GÕÕ values, decreasing again for the 6.6 μM AP sample.…”

Peptide hydrogel in vitro non‐inflammatory potential

“…A number of molecular designs have been developed for the synthesis of self‐assembling peptide LMWHs with the four main families being amphiphilic peptides, 13, 14, 15 short peptide derivatives, 16, 17, 18, 19, 20 α ‐helix/coil‐coil peptides 21, 22 and β ‐sheet peptides. 4, 23, 24, 25, 26, 27, 28, 29 β ‐sheet peptides are of particular interest as they allow the fabrication of very stable hydrogels with properties that can be tailored through peptide design, media properties and processing.…”

Supramolecular Hydrogels Made of Basic Biological Building Blocks

“…That is, hydrogelator 35 forms well-defined β-sheets with a cross-β X-ray diffraction pattern, while hydrogelator 36 forms un-oriented assemblies with multiple stacked sheets. [96] The switch of the K and V residues in 35 and 36 not only changes the peptidic backbones, but also alter the distribution of the hydrophobic groups. It is possible that the latter has a more pronounced effect on the self-assembled structures.…”