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

Area of Science:

• Biomaterials Science
• Supramolecular Chemistry
• Computational Biology

Background:

• Cyclic peptides with disc-shaped structures are key for novel biomaterials.
• Understanding their self-assembly is crucial for material design.

Purpose of the Study:

• To investigate the self-assembling properties of novel cyclic peptides composed of alternating α-residues and cyclic δ-amino acids (α,δ-CPs).
• To explore the stacking preferences and structural stability of these α,δ-CPs.
• To compare the assembly behavior of α,δ-CPs with α,γ-CPs.

Main Methods:

• Synergistic in vitro and in silico analysis using dimeric models and nanotubes.
• Computational modeling to examine parallel and antiparallel stacking interactions.
• Comparative analysis of α,δ-CPs and α,γ-CPs assembly.

Main Results:

• α,δ-CPs can adopt both parallel and antiparallel stacking.
• Parallel β-sheet structures are generally more stable but can be switched to antiparallel.
• α,γ-CPs unexpectedly favor parallel β-sheet structures, contrary to prior assumptions.

Conclusions:

• The study reveals a new paradigm for designing cyclic peptides, emphasizing the role of specific residue interactions in controlling assembly.
• Findings suggest that skeleton interactions, not just cross-strand interactions, dictate β-sheet formation in α,γ-CPs.
• Results have significant implications for the rational design of cyclic peptide-based dimers and nanotubes for advanced biomaterials.