Formation of functional super-helical assemblies by constrained single heptad repeat

Abstract

Inspired by the key role of super-helical motifs in molecular self-organization, several tandem heptad repeat peptides were used as building blocks to form well-ordered supramolecular nano-assemblies. However, the need for stable helical structures limits the length of the smallest described units to three heptad repeats. Here we describe the first-ever self-assembling single heptad repeat module, based on the ability of the non-coded α-aminoisobutyric acid to stabilize very short peptides in helical conformation. A conformationally constrained peptide comprised of aromatic, but not aliphatic, residues, at the first and fourth positions formed helical fibrillar assemblies. Single crystal X-ray analysis of the peptide demonstrates super-helical packing in which phenylalanine residues formed an ‘aromatic zipper' arrangement at the molecular interface. The modification of the minimal building block with positively charged residues results in tight DNA binding ascribed to the combined factors of helicity, hydrophobicity and charge. The design of these peptides defines a new direction for assembly of super-helical nanostructures by minimal molecular elements.

A minimal length rigid helical peptide motif allows rational design of modular surfactants

“…Recently, we reported the solution state morphology and solid-state structure of the peptide SHR-FF (H 2 N-Ser-Aib-Phe-Ser-Aib-Phe-Aib-OH; Fig. 1a), containing α-aminoisobutyric acid residues (Aib)26. We observed that all the amino acid residues, except phenylalanine (Phe), adopted dihedral angles in accordance with a Ramachandran plot of a 3 10 helix26.…”

“…1a), containing α-aminoisobutyric acid residues (Aib)26. We observed that all the amino acid residues, except phenylalanine (Phe), adopted dihedral angles in accordance with a Ramachandran plot of a 3 10 helix26. The discrepancy in dihedral angles of Phe prompted us to refine the original design by modifying SHR-FF.…”

Charge‐Induced Secondary Structure Transformation of Amyloid‐Derived Dipeptide Assemblies from β‐Sheet to α‐Helix

“…[20] On the contrary,n oi ntramolecular interactions exist in the neutral Fmoc-FF.Next, we studied the molecular mechanism underlying the distinctive self-assembly behaviors of Fmoc-FF with different charged states using all-atom molecular dynamics (AAMD) simulations. [20] On the contrary,n oi ntramolecular interactions exist in the neutral Fmoc-FF.Next, we studied the molecular mechanism underlying the distinctive self-assembly behaviors of Fmoc-FF with different charged states using all-atom molecular dynamics (AAMD) simulations.…”

“…Zuschriften formation of helical structures. [20] On the contrary,n oi ntramolecular interactions exist in the neutral Fmoc-FF.Next, we studied the molecular mechanism underlying the distinctive self-assembly behaviors of Fmoc-FF with different charged states using all-atom molecular dynamics (AAMD) simulations. [21] After 50 ns AAMD simulations,itis obvious that the Fmoc-FF nanofibril almost keep the antiparallel b-sheet conformation, indicating such as econdary structure is energetically favorable for the Fmoc-FF assemblies with lowcharged state.I ns harp contrast, the starting model for the negatively charged Fmoc-FF À becomes quickly unstable and undergoes as tructural transition from ap arallel b-sheet to ahelix-featured morphology (Figure 3c and d).…”

The Helix to Super‐Helix Transition in the Self‐Assembly of π‐Systems: Superseding of Molecular Chirality at Hierarchical Level

“…[2][3][4][5][6] Tr ansfer of chirality can takes place from 1) single molecules to one-dimensional (1D) assemblies and then from 2) 1D helical assemblies to macroscopic superstructures.I np rinciple,e ach step in this propagation process can determine the overall supramolecular chirality of the system and therefore sometimes creates ambiguity in predicting the handedness of helical assemblies. [2][3][4][5][6] Tr ansfer of chirality can takes place from 1) single molecules to one-dimensional (1D) assemblies and then from 2) 1D helical assemblies to macroscopic superstructures.I np rinciple,e ach step in this propagation process can determine the overall supramolecular chirality of the system and therefore sometimes creates ambiguity in predicting the handedness of helical assemblies.…”