Disassembling peptide-based fibres by switching the hydrophobic-hydrophilic balance.

Amyloid-like model peptides, modified on the N-terminus with an alkyl tail and on the C-terminus with a PEG chain, yielded fibres that were susceptible to triggered disassembly by removal of the alkyl chain, which affected the hydrophobic-hydrophilic balance.

Self-assembled gels for biomedical applications.

Natural and synthetic gel-like materials have featured heavily in the development of biomaterials for wound healing and other tissue-engineering purposes. More recently, molecular gels have been designed and tailored for the same purpose. When mixed with, or conjugated to therapeutic drugs or bioactive molecules, these materials hold great promise for treating/curing life-threatening and degenerative diseases, such as cancer, osteoarthritis, and neural injuries. This focus review explores the latest advances in this field and concentrates on self-assembled gels formed under aqueous conditions (i.e., self-assembled hydrogels), and critically compares their performance within different biomedical applications, including three-dimensional cell-culture studies, drug delivery, and tissue engineering. Although stability and toxicity issues still need to be addressed in more detail, it is clear from the work reviewed here that self-assembled gels have a bright future as novel biomaterials.

Controlled disassembly of peptide amphiphile fibres.

In this paper, the introduction of both a methionine residue and a nitrobenzyl derivative as a labile linker between the peptide part and the hydrophobic alkyl chain of a peptide amphiphile are presented. These modifications are shown not to inhibit the formation of structured assemblies that analogous peptide amphiphiles lacking the linkers are able to form. Moreover, the introduction of either labile linker allows removal of the peptide amphiphile's stabilizing hydrophobic moieties to initiate a controlled disassembly of fibre aggregates. This is achieved by either treatment with CNBr or UV irradiation, respectively. These disassembly mechanisms could be the starting point for methodology that allows further manipulation of self-assembled peptide amphiphile architectures.

Stabilization of peptide fibrils by hydrophobic interaction.

Hydrophobic interactions play an important role in assembly processes in aqueous environments. In case of peptide amphiphiles, hydrophobicity is combined with hydrogen bonding to yield well-defined peptide-based aggregates. Here, we report a systematic study after the role of hydrophobic interactions on both stabilization and morphology of a peptide fibrillar assembly. For this purpose, alkyl tails were connected to a known beta-sheet forming peptide with the sequence KTVIIE. The introduction of n-alkyl groups induced thermal stability to the assemblies without affecting the morphology of the peptide aggregates.

Solid-phase synthesis of C-terminally modified peptides.

In this paper, a straightforward and generic protocol is presented to label the C-terminus of a peptide with any desired moiety that is functionalized with a primary amine. Amine-functional molecules included are polymers (useful for hybrid polymers), long alkyl chains (used in peptide amphiphiles and stabilization of peptides), propargyl amine and azido propyl-amine (desirable for 'click' chemistry), dansyl amine (fluorescent labeling of peptides) and crown ethers (peptide switches/hybrids). In the first part of the procedure, the primary amine is attached to an aldehyde-functional resin via reductive amination. To the secondary amine that is produced, an amino acid sequence is coupled via a standard solid-phase peptide synthesis protocol. Since one procedure can be applied for any given amine-functional moiety, a robust method for C-terminal peptide labeling is obtained.

Tuning secondary structure and self-assembly of amphiphilic peptides.

Self-assembly is one of nature's mechanisms by which higher order structures are obtained. Two of the main driving forces for self-assembly, hydrophobic interactions and hydrogen bonding, are both present within amphiphilic peptides. Here, it is demonstrated how the intricately interconnected folding and assembly behavior of an N-terminally acylated peptide, with the sequence GANPNAAG, has been tuned by varying its hydrophobic tail and thermal history. The change in interplay between hydrophobic forces and peptide folding allowed the occurrence of different types of aggregation, from soluble peptides with a random coil conformation to aggregated peptides arranged in a beta-sheet assembly, which form helically twisted bilayer ribbons.