Enzymatically-stable oxetane-based dipeptide hydrogels

Abstract

Low molecular weight gelators that are not easily degraded by enzymes have a range of potential applications. Here, we report new Fmoc-protected dipeptides in which the amide carbonyl group has been replaced by an oxetane ring. Remarkably one of these peptidomimetics, but not the corresponding dipeptide, is an effective gelator, forming hydrogels at a concentration of 3 mg mL. On assembly, there is a lack of beta-sheet structure, implying that there is no requirement for this motif in such a gel. Furthermore, the modified dipeptide is also stable to proteolysis compared to the parent dipeptide.

Self-assembly and hydrogel formation ability of Fmoc-dipeptides comprising α-methyl-L-phenylalanine

“…Moreover, Moretto and coworkers developed unique peptides containing ααAA, which have two azobenzene moieties as side chains that are capable of participating in the photoresponsive transformations of supramolecular nanostructures [24]. Due to limited examples [25,26], the systematic construction of peptides containing ααAAs and the investigation of their selfassembly are significant in understanding the influence of subtle but precise chemical modifications of constituent peptides on the ability of these peptides to form supramolecular nanostructures.…”

Unravelling the 2D self-assembly of Fmoc-dipeptides at fluid interfaces

“…Dipeptides are an exciting building block in nanotechnology. [1][2][3][4][5][6][7][8] Dipeptides display some advantageous features among selfassembling organic molecules, such as easy choice in sequence during synthesis, readily available chiral features and high biocompatibility, with Fmoc-dipeptides as highly promising structure, especially in biological applications. 9 Intracellular NO delivery was achieved by a purposefully self-assembling dipeptide.…”

Using Peptidomimetics and Constrained Peptides as Valuable Tools for Inhibiting Protein–Protein Interactions

“…They often lack the ability to fold into their bioactive conformation because of an entropic penalty for folding and they are susceptible to faster rates of degradation due to proteolysis. Overcoming these difficulties frequently involves one or more of the following: incorporation of non-native amino acids [ 53 ], D-amino acids [ 54 , 55 , 56 , 57 ], and β-amino acids [ 58 ]; retro-inverso peptides [ 59 ]; changing the backbone (through N -methylation [ 60 ], or the introduction of amide bond isosteres [ 61 ]); and cyclising strategies [ 62 , 63 , 64 , 65 ]. Non-native amino acids confer stability as a result of the proteolytic machinery in the cell being ill equipped to deal with unnatural amino acids [ 66 ].…”