The Phe-Phe Motif for Peptide Self-Assembly in Nanomedicine

Abstract

Since its discovery, the Phe-Phe motif has gained in popularity as a minimalist building block to drive the self-assembly of short peptides and their analogues into nanostructures and hydrogels. Molecules based on the Phe-Phe motif have found a range of applications in nanomedicine, from drug delivery and biomaterials to new therapeutic paradigms. Here we discuss the various production methods for this class of compounds, and the characterization, nanomorphologies, and application of their self-assembled nanostructures. We include the most recent findings on their remarkable properties, which hold substantial promise for the creation of the next generation nanomedicines.

Keywords: diphenylalanine; hydrogels; nanostructures; peptides; self-assembly.

Figure 1

Simple compounds bearing the Phe-Phe motif self-assemble into diverse nanomorphologies. Scale bars = 100 nm, unless otherwise stated on the image. Adapted with permission from: refs. [13,55] © 2012 American Chemical Society; refs. [36,54,56] with kind permission of the Royal Society of Chemistry; ref. [39] with permission from Wiley © 2008 WILEY-VCH Verlag GmbH & Co. KGaA; and with permission from ref. [57] © 2006 Nature Publishing Group.

Figure 2

Chemical structure of a self-assembling peptide derivative covalently linked to taxol and formed upon phosphatase conversion of a phosphate precursor (top); upon self-assembly, a nanostructured hydrogel was formed and the IC₅₀ calculated (bottom). Adapted with permission from ref. [63] © 2013 American Chemical Society.

Figure 3

Rhodamine B actively participates in the assembly process of a tripeptide to yield a self-supportive hydrogel (A). Confocal fluorescence microscopy highlights the presence of the dye in the supramolecular structures (B); resulting in different circular dichroism spectra relative to the peptide alone (C) [68].

Figure 4

Enzyme catalyzed formation pericellular hydrogel/nanonets to induce cell death. Adapted with permission from ref. [75], Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA.