Parallel Versus Antiparallel ß-Sheet Structure in Cyclic Peptide Hybrids Containing γ- or δ-Cyclic Amino Acids.

Cyclic peptides with disc-shaped structures have emerged as potent building blocks for the preparation of new biomaterials in fields ranging from biological to material science. In this work, we analyze in depth the self-assembling properties of a new type of cyclic peptides based on the alternation of α-residues and cyclic δ-amino acids (α,δ-CPs). To examine the preferred stacking properties adopted by cyclic peptides bearing this type of amino acids, we carried out a synergistic in vitro/in silico approximation by using simple dimeric models and then extended to nanotubes. Although these new cyclic peptides (α,δ-CPs) can interact either in a parallel or antiparallel fashion, our results confirm that although the parallel ß-sheet is more stable, it can be switched to the antiparallel stacking by choosing residues that can establish favorable cross-strand interactions. Moreover, the subsequent comparison by using the same methodology but applied to α,γ-CPs models, up to the moment assumed as antiparallel-like d,l-α-CPs, led to unforeseen conclusions that put into question preliminary conjectures about these systems. Surprisingly, they tend to adopt a parallel ß-sheet directed by the skeleton interactions. These results imply a change of paradigm with respect to cyclic peptide designs that should be considered for dimers and nanotubes.

Self-Sorting of cyclic peptide homodimers into a heterodimeric assembly featuring an efficient photoinduced intramolecular electron-transfer process.

We describe the thermodynamic characterisation of the self-sorting process experienced by two homodimers assembled by hydrogen-bonding interactions through their cyclopeptide scaffolds and decorated with Zn-porphyrin and fullerene units into a heterodimeric assembly that contains one electron-donor (Zn­porphyrin) and one electron-acceptor group (fullerene). The fluorescence of the Zn-porphyrin unit is strongly quenched upon heterodimer formation. This phenomenon is demonstrated to be the result of an efficient photoinduced electron-transfer (PET) process occurring between the Zn-porphyrin and the fullerene units of the heterodimeric system. The recombination lifetime of the charge-separated state of the heterodimer complex is in the order of 180 ns. In solution, both homo- and heterodimers are present as a mixture of three regioisomers: two staggered and one eclipsed. At the concentration used for this study, the high stability constant determined for the heterodimer suggests that the eclipsed conformer is the main component in solution. The application of the bound-state scenario allowed us to calculate that the heterodimer exists mainly as the eclipsed regioisomer (75-90 %). The attractive interaction that exists between the donor and acceptor chromophores in the heterodimeric assembly favours their arrangement in close contact. This is confirmed by the presence of charge-transfer bands centred at 720 nm in the absorption spectrum of the heterodimer. PET occurs in approximately 75% of the chromophores after excitation of both Zn-porphyrin and fullerene chromophores. Conversely, analogous systems, reported previously, decorated with extended tetrathiafulvalene and fullerene units showed a PET process in a significantly reduced extent (33%). We conclude that the strength (stability constant (K) x effective molarity (EM)) of the intramolecular interaction established between the two chromophores in the Zn-porphyrin/fullerene cyclopeptide-based heterodimers controls the regioisomeric distribution and regulates the high extent to which the PET process takes place in this system.

Self-assembling properties of all γ-cyclic peptides containing sugar amino acid residues.

In this study, a novel dimer-forming cyclic peptide composed exclusively by cyclic γ-amino acids with a saccharide-like outer surface is described. The antiparallel ß-sheet type hydrogen bonding interactions responsible for the large association constant in non-polar solvents constitute a suitable model for a novel class of self-assembling peptide nanotubes.

New self-assembling peptide nanotubes of large diameter using δ-amino acids.

Here we show that 4-aminocyclohexanecarboxylic acid is a rigid stretcher building block for the preparation of cyclic peptides that self-assemble to form peptide nanotubes with large diameter and hydrophobic pores. The hydrophobic properties of the resulting nanotubes provided by the two methylene groups per δ-residue allow the encapsulation of C60 moieties forming a new type of bionanopeapod structure.

Membrane-targeted self-assembling cyclic peptide nanotubes.

Peptide nanotubes are novel supramolecular nanobiomaterials that have a tubular structure. The stacking of cyclic components is one of the most promising strategies amongst the methods described in recent years for the preparation of nanotubes. This strategy allows precise control of the nanotube surface properties and the dimensions of the tube diameter. In addition, the incorporation of 3- aminocycloalkanecarboxylic acid residues in the nanotube-forming peptides allows control of the internal properties of the supramolecular tube. The research aimed at the application of membrane-interacting self-assembled cyclic peptide nanotubes (SCPNs) is summarized in this review. The cyclic peptides are designed to interact with phospholipid bilayers to induce nanotube formation. The properties and orientation of the nanotube can be tuned by tailoring the peptide sequence. Hydrophobic peptides form transmembrane pores with a hydrophilic orifice, the nature of which has been exploited to transport ions and small molecules efficiently. These synthetic ion channels are selective for alkali metal ions (Na(+), K(+) or Cs(+)) over divalent cations (Ca(2+)) or anions (Cl(-)). Unfortunately, selectivity was not achieved within the series of alkali metal ions, for which ion transport rates followed the diffusion rates in water. Amphipathic peptides form nanotubes that lie parallel to the membrane. Interestingly, nanotube formation takes place preferentially on the surface of bacterial membranes, thus making these materials suitable for the development of new antimicrobial agents.