Is a cross-β-sheet structure of low molecular weight peptides necessary for the formation of fibrils and peptide hydrogels?

Abstract

Short peptides have emerged as versatile building blocks for supramolecular structures and hydrogels. In particular, the presence of aromatic amino acid residues and/or aromatic end groups is generally considered to be a prerequisite for initiating aggregation of short peptides into nanotubes or cross β-sheet type fibrils. However, the cationic GAG tripeptide surprisingly violates these rules. Specifically, in water/ethanol mixtures, GAG peptides aggregate into very long crystalline fibrils at temperatures below 35 °C where they eventually form a spanning network structure and, thus, a hydrogel. Two gel phases are formed in this network, and they differ substantially in chirality and thickness of the underlying fibrils, their rheological parameters, and the kinetics of oligomerization, fibrilization, and gel formation. The spectroscopic data strongly suggests that the observed fibrils do not exhibit canonical cross β-sheet structures and are indicative of a yet unknown secondary conformation. To complement our unusual experimental observations in this perspective article, we performed large-scale DFT calculations to probe the geometry and spectroscopic properties of these GAG oligomers. Most importantly, our experimental and computational results yield rather unconventional structures that are not reminiscent of classical cross-β-sheet structures, and we give two extremely likely candidates for oligomer structures that are consistent with experimental amide I' profiles in IR and vibrational circular dichroism (VCD) spectra of the two gel phases.

The impact of thermal history on the structure of glycylalanylglycine ethanol/water gels

“…This is consistent with expected distances between strands of a β‐sheet or between β‐sheets in stacks, respectively 32 . This does not necessarily mean that the fibrils form β‐sheets, similar distances can be expected for alternative arrangements 31 …”

“…The powder and fibril spectra show a sharp split of the amide I profile into bands at 1644 cm −1 (AI 1 ) and 1673 cm −1 (AI 2 ). For the peptide powder, the peak intensity for AI 1 is twice that of the AI 2 peak intensity, which indicates substantial excitonic coupling between individual amide I modes and thus a rather high degree of molecular order 31 . The fibrils' spectrum shows a qualitatively similar doublet but a reduced peak intensity ratio (i.e., AI 1 /AI 2 = 1.2 for phase I and slightly below 1 for phase II).…”

Evaluation of various methods of selection of B. subtilis strains capable of secreting surface-active compounds

“…It would also be possible to calculate the effect of biosurfactant addition on the interfacial tension in a two-phase system and to estimate lateral and rotational diffusion of the peptide ring [68]. Studies on the use of biomolecules such as surfactin can also be supplemented with modeling of molecular structure using density functional theory (DFT), which includes dispersion interactions and peptide bonds in peptide-based systems [69].…”

A new interpretation of the structure and solvent dependence of the far UV circular dichroism spectrum of short oligopeptides

“…17 For the present study we used the optimized geometry of these two conformations in TDDFT calculations at the ωB97X-D/cc-pVTZ level of theory to calculate the UVCD and corresponding absorption spectra of GAG in implicit and explicit water. 17 We specifically chose the ωB97X-D functional for our studies since it contains an asymptoticallycorrect (range-separated) portion of nonlocal exchange in conjunction with dispersion corrections, which are essential for accurately predicting charge-transfer excitations and hydrogenbonding interactions, 18 respectively. It is also important to note that prior work by Neto et al 19 has shown that the optimal range-separated parameter, ω, required to accurately predict excited-states in explicit solvent is 0.25, which is already close to the default value of ω = 0.2 used in the ωB97X-D functional.…”