The self‐assembly of a dehydrophenylalanine containing dipeptide (see figure), yielding highly ordered nanotubular structures, is discussed. The tubes are longer and thinner than previously reported peptide‐based tubular structures; they are stable to boiling‐water temperatures, different pH conditions, and to a highly nonspecific protease (Proteinase K).

Bottom-up fabrication by molecular self-assembly is now widely recognized as a potent method for generating interesting and functional nano- and mesoscale structures. Hydrogels from biocompatible molecules are an interesting class of mesoscale assemblies with potential biomedical applications. The self-assembly of a proteolysis resistant aromatic dipeptide containing a conformational constraining residue (DeltaPhe) into a stable hydrogel has been studied in this work. The reported dipeptide has free -N and -C termini. The hydrogel was self-supportive, was fractaline in nature, and possessed high mechanical strength. It was responsive to environmental conditions like pH, temperature, and ionic strength. The gel matrix could encapsulate and release bioactive molecules in a sustained manner. The described hydrogel showed no observable cytotoxicity to the HeLa and L929 cell lines in culture.

Peptide-based vesicular structures have been the focus of research in the past decade for their potential application as drug delivery agents. We here report the self-assembly of amphiphilic dipeptides containing conformation-constraining alpha,beta-dehydrophenylalanine into nanovesicles. The vesicles can encapsulate small drug molecules such as riboflavin and vitamin B(12), bioactive peptides, and small protein molecules. The nanovesicles are resistant to treatment of a nonspecific protease, proteinase K, and are stable at low concentrations of monovalent and divalent cations. The vesicles are effectively taken up by actively growing cells in culture and show no observable cytopathic effects. These peptide-based nanostructures can be considered as models for further development as delivery agents for different biomolecules.

Three-dimensional (3D) hydrogels incorporating a compendium of bioactive molecules can allow efficient proliferation and differentiation of cells and can thus act as successful tissue engineering scaffolds. Self-assembled peptide-based hydrogels can be worthy candidates for such applications as peptides are biocompatible, biodegradable and can be easily functionalized with desired moieties. Here, we report 3D growth and proliferation of mammalian cells (HeLa and L929) on a dipeptide hydrogel chemically functionalized with a pentapeptide containing Arg-Gly-Asp (RGD) motif. The method of functionalization is simple, direct and can be adapted to other functional moieties as well. The functionalized gel was noncytotoxic, exhibited enhanced cell growth promoting properties, and promoted 3D growth and proliferation of cells for almost 2 weeks, with simultaneous preservation of their metabolic activities. The presence of effective cell growth supporting properties in a simple and easy to functionalize dipeptide hydrogel is unique and makes it a promising candidate for tissue engineering and cell biological applications.