Stability of Protein Structure during Nanocarrier Encapsulation: Insights on Solvent Effects from Simulations and Spectroscopic Analysis.

The dosing of peptide and protein therapeutics is complicated by rapid clearance from the blood pool and poor cellular membrane permeability. Encapsulation into nanocarriers such as liposomes or polymersomes has long been explored to overcome these limitations, but manufacturing challenges have limited clinical translation by these approaches. Recently, inverse Flash NanoPrecipitation (iFNP) has been developed to produce highly loaded polymeric nanocarriers with the peptide or protein contained within a hydrophilic core, stabilized by a hydrophobic polymer shell.

Harnessing synthetic biology to enhance heterologous protein expression.

The ability to express heterologous proteins in microbial hosts is crucial for many areas of research and technology. In most cases, however, successful expression and purification of the desired protein require fusion to another protein. To date, all fusion partners have been chosen from natural sequences, which evolved for other purposes, and may not be optimal fusion partners.

Are natural proteins special? Can we do that?

Natural proteins represent a minuscule fraction of possible sequence space. These very rare sequences display remarkable properties: They fold into many different stable structures, and perform a wide range of complex biological functions. These two considerations-rarity and functionality-may suggest that natural proteins are somehow special.

Correction: Stacking interactions by two Phe side chains stabilize and orient assemblies of even the minimal amphiphilic β-sheet motif.

Correction for 'Stacking interactions by two Phe side chains stabilize and orient assemblies of even the minimal amphiphilic β-sheet motif' by Shlomo Zarzhitsky et al., Chem. Commun.

Stacking interactions by two Phe side chains stabilize and orient assemblies of even the minimal amphiphilic β-sheet motif.

Here we demonstrate that the smallest possible motif of the amphiphilic and pleated β-strand structure can be generated using tri-peptides stabilized by π-π stacking interactions. Monitoring the early stages of Phe-Glu-Phe fibril formation revealed unique angular orientations. Phe-Glu-Phe fibrils were further exploited as adsorbing templates for metal ions.

Transparent, conductive, and SERS-active Au nanofiber films assembled on an amphiphilic peptide template.

The use of biological materials as templates for functional molecular assemblies is an active research field at the interface between chemistry, biology, and materials science. We demonstrate the formation of gold nanofiber films on β-sheet peptide domains assembled at the air/water interface. The gold deposition scheme employed a recently discovered chemical process involving spontaneous crystallization and reduction of water-soluble Au(SCN)4(1-) upon anchoring to surface-displayed amine moieties.

The effect of pH and calcium ions on the stability of amphiphilic and anionic β-sheet peptide hydrogels.

Amphiphilic peptides can form bottom-up-designed self-assembled hydrogels composed of elongated fibril matrices that could find uses in various biologically-related systems, acting as platforms for drug delivery or scaffolds that mimic extracellular matrices in tissue regeneration systems. We have previously reported that the amphiphilic and anionic β-sheet forming peptide, Pro-Asp-(Phe-Asp)5 -Pro, P(FD)-5, generates hydrogels that template calcium-phosphate mineral and as such, were able to enhance bone formation in vivo. Our earlier results prompted us to further exploit the effects of pH and calcium ion concentration on P(FD)-5 peptide in solution, in hydrogels and in mineral-loaded hydrogel compositions.

Acidic peptide hydrogel scaffolds enhance calcium phosphate mineral turnover into bone tissue.

Designed peptides may generate molecular scaffolds in the form of hydrogels to support tissue regeneration. We studied the effect of hydrogels comprising β-sheet-forming peptides rich in aspartic amino acids and of tricalcium phosphate (β-TCP)-loaded hydrogels on calcium adsorption and cell culture in vitro, and on bone regeneration in vivo. The hydrogels were found to act as efficient depots for calcium ions, and to induce osteoblast differentiation in vitro.

The interactions between doxorubicin and amphiphilic and acidic β-sheet peptides towards drug delivery hydrogels.

Amphiphilic β-sheet peptides decorated by acidic amino acids may spontaneously assemble into ordered monolayers at interfaces as well as form hydrogels at near physiological pH values. Here we monitored interactions between the peptide Pro-Asp-(Phe-Asp)(5)-Pro and the mildly amphiphilic chemotherapeutic drug doxorubicin (Dox). The peptide in the form of monolayers at the air water interface was found to enhance Dox adsorption, pointing to favorable interactions between the amphiphilic peptide and Dox.