Design of Chiral β-Double Helices from γ-Peptide Foldamers.

Chirality is ubiquitous in nature, and homochirality is manifested in many biomolecules. Although β-double helices are rare in peptides and proteins, they consist of alternating L- and D-amino acids. No peptide double helices with homochiral amino acids have been observed.

A cationic amphiphilic peptide chaperone rescues Aβ aggregation and cytotoxicity.

Directing Aβ to adopt a conformation that is free from aggregation and cell toxicity is an attractive and viable strategy to design therapeutics for Alzheimer's disease. Over the years, extensive efforts have been made to disrupt the aggregation of Aβ using various types of inhibitors but with limited success. Herein, we report the inhibition of aggregation of Aβ and disintegration of matured fibrils of Aβ into smaller assemblies by a 15-mer cationic amphiphilic peptide.

Structural insight into hybrid peptide ε-helices.

Unique ε-helical organizations (11-helices) from β,γ-hybrid peptides composed of chiral β-amino acids along with achiral 3,3- or 4,4-dimethyl substituted γ-amino acids are disclosed.

Structural Investigation of Hybrid Peptide Foldamers Composed of α-Dipeptide Equivalent β-Oxy-δ -amino Acids.

Due to their equivalent lengths, δ-amino acids can serve as surrogates of α-dipeptides. However, δ-amino acids with proteinogenic side chains have not been well studied because of synthetic difficulties and because of their insolubility in organic solvents. Recently we reported the spontaneous supramolecular gelation of δ-peptides composed of β(O)-δ -amino acids.

Ambidextrous α,γ-Hybrid Peptide Foldamers.

Molecular chirality is ubiquitous in nature. The natural biopolymers, proteins and DNA, preferred a right-handed helical bias due to the inherent stereochemistry of the monomer building blocks. Here, we are reporting a rare co-existence of left- and right-handed helical conformations and helix-terminating property at the C-terminus within a single molecule of α,γ-hybrid peptide foldamers composed of achiral Aib (α-aminoisobutyric acid) and 3,3-dimethyl-substituted γ-amino acid (Adb; 4-amino-3,3-dimethylbutanoic acid).

Structural Dimorphism of Achiral α,γ-Hybrid Peptide Foldamers: Coexistence of 12- and 15/17-Helices.

Here, novel 12-helices in α,γ-hybrid peptides composed of achiral α-aminoisobutyric acid (Aib) and 4-aminoisocaproic acid (Aic, doubly homologated Aib) monomers in 1:1 alternation are reported. The 12-helices were indicated by solution and crystal structural analyses of tetra- and heptapeptides. Surprisingly, single crystals of the longer nonapeptide displayed two different helix types: the novel 12-helix and an unprecedented 15/17-helix.

Homooligomeric β (R)-valine peptides: Transformation between C and C helical structures induced by a guest Aib residue.

Novel helical, structures unprecedented in the chemistry of α-polypeptides, may be found in polypeptides containing β and γ amino acids. The structural characterization of C and C -helices in oligo β-peptides was originally achieved using conformationally constrained cyclic β-residues. This study explores the conformational characteristics of proteinogenic β residues in homooligomeric sequences and addresses the issue of inducing a transition between C and C helices by the introduction of a guest α-residue.

Exploring structural features of folded peptide architectures in the construction of nanomaterials.

We are reporting the influence of foldamer structures on their self-assembled architectures. In a sharp contrast to the ordered α,γ-hybrid 12-helix obtained from 1 : 1 alternating Aib and γ-Phe, the α,γ-hybrid peptides constituted with α-Phe and 4,4-dimethyl γ-amino acid (Aic) displayed the extended sheet type of conformations in solution and spontaneously self-assembled into thermally and proteolytically stable capsules. In contrast, the conformationally ordered 12-helix self-assembled into a three-dimensional supramolecular polyhedron.