Self‐Assembly of a Dipeptide‐ Containing Conformationally Restricted Dehydrophenylalanine Residue to Form Ordered Nanotubes

Abstract

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).

Self-assembly of diphenylalanine with preclick components as capping groups

“…conformation. 65,66 In all cases these structural characteristics are preserved between -50 ºC and +60 ºC, as is demonstrated by the spectra acquired at different temperatures within such interval ( Figure S3). …”

Novel dipeptide nanoparticles for effective curcumin delivery

“…[22][23][24][25][26][27] Several reports, including our own studies, have shown that dipeptides, either free or with N-or C-terminal modifications, can self-assemble into well-defined NPs. 18,19,[28][29][30] However, most of these studies have shown assembly in an aqueous environment and may not be suitable for delivering hydrophobic bioactive molecules. Thus, we attempted to develop dipeptide-based nanostructures, which can be prepared in organic or aqueous-organic environments, for potential loading of hydrophobic drugs.…”

“…19,29 Although this solvent is excellent for dissolving peptides, it may not be suitable if the self-assembled structures are to be developed for in vivo studies due to high toxicity. 31 Therefore, we sought to replace HFIP with a more suitable solvent.…”

“…Since curcumin is soluble and retains all of its activities in methanol, 32,33 which is a pharmaceutically acceptable solvent and has been used to prepare various drug nanoformulations, 34,35 we first investigated whether ∆Phe-containing dipeptides would self-assemble in methanol. For this purpose, we selected previously described self-assembling dehydrodipeptides, such as phenylalanine-dehydrophenylalanine (F∆F), glutamic acid-dehydrophenylalanine (E∆F), and lysinedehydrophenylalanine (K∆F) 18,19,29 as well as newly synthesized molecules such as M∆F, I∆F, and L∆F (Table S1) and examined their assembly behavior using DLS. Surprisingly, none of these peptides assembled in neat methanol; however, all assembled when their HFIP solution was diluted with water.…”

“…42,49,50 Generally dipeptide NPs are obtained by the process of molecular self-assembly, mainly driven by noncovalent interactions such as van der Waals, electrostatic, and hydrophobic interactions as well as hydrogen bonds. 19,29,51 Hydrophobic interactions in particular can play a crucial role in stabilizing peptide-based nanostructures. 52,53 Thus, it is possible that curcumin, a hydrophobic molecule, may influence the assembly and overall morphology of M∆F nanoparticles.…”