Surfactant-induced assembly of enzymatically-stable peptide hydrogels.

The secondary structure of peptides in the presence of interacting additives is an important topic of study, having implications in the application of peptide science to a broad range of modern technologies. Surfactants constitute a class of biologically relevant compounds that are known to influence both peptide conformation and aggregation or assembly. We have characterized the secondary structure of a linear nonapeptide composed of a hydrophobic alanine/phenylalanine core flanked by hydrophilic acid/amine units. We show that the anionic surfactant sodium dodecyl sulfate (SDS) induces the formation of ß-sheets and macroscopic gelation in this otherwise unstructured peptide. Through comparison to related additives, we propose that SDS-induced secondary structure formation is the result of amphiphilicity created by electrostatic binding of SDS to the peptide. In addition, we demonstrate a novel utility of surfactants in manipulating and stabilizing peptide nanostructures. SDS is used to simultaneously induce secondary structure in a peptide and to inhibit the activity of a model enzyme, resulting in a peptide hydrogel that is impervious to enzymatic degradation. These results complement our understanding of the behavior of peptides in the presence of interacting secondary molecules and provide new potential pathways for programmable organization of peptides by the addition of such components.

Supramolecular assembly of asymmetric self-neutralizing amphiphilic peptide wedges.

Mimicking the remarkable dynamic and multifunctional utility of biological nanofibers, such as microtubules, is a challenging and technologically attractive objective in synthetic supramolecular chemistry. Understanding the complex molecular interactions that govern the assembly of synthetic materials, such as peptides, is key to meeting this challenge. Using molecular dynamics simulations to guide molecular design, we explore here the self-assembly of structurally and functionally asymmetric wedge-shaped peptides. Supramolecular assembly into nanofiber gels or multilayered lamellar structures was determined by cooperative influences of hydrogen bonding, amphiphilicity (hydrophilic asymmetry), and the distribution of electrostatic charges on the aqueous self-assembly of asymmetric peptides. Molecular amphiphilicity and ß-sheet forming capacity were both identified as necessary, but not independently sufficient, to form supramolecular nanofibers. Imbalances in positive and negative charges prevented nanofiber assembly, while the asymmetric distribution of balanced charges within a peptide is believed to affect peptide conformation and subsequent self-assembly into either nanofibers or lamellar structures. Insights into cooperative molecular interactions and the effects of molecular asymmetry on assembly may aid the development of next-generation supramolecular nanomaterial assemblies.

A multi-stimuli responsive, self-assembling, boronic acid dipeptide.

Modification of the dipeptide of phenylalanine, FF, with a boronic acid (BA) functionality imparts unique aqueous self-assembly behavior that responds to multiple stimuli. Changes in pH and ionic strength are used to trigger hydrogelation via the formation of nanoribbon networks. Furthermore, we show for the first time that the binding of polyols to the BA functionality can modulate a peptide between its assembled and disassembled states.

Thermally programmable pH buffers.

Many reactions in both chemistry and biology rely on the ability to precisely control and fix the solution concentrations of either protons or hydroxide ions. In this report, we describe the behavior of thermally programmable pH buffer systems based on the copolymerization of varying amounts of acrylic acid (AA) groups into N-isopropylacrylamide polymers. Because the copolymers undergo phase transitions upon heating and cooling, the local environment around the AA groups can be reversibly switched between hydrophobic and hydrophilic states affecting the ionization behavior of the acids. Results show that moderate temperature variations can be used to change the solution pH by two units. However, results also indicate that the nature of the transition and its impact on the pH values are highly dependent on the AA content and the degree of neutralization.