Facile and Precise Formation of Unsymmetric Vesicles Using the Helix Dipole, Stereocomplex, and Steric Effects of Peptides

Unsymmetrical vesicular membranes were prepared from a binary mixture of the A₃B-type and the AB-type host polypeptides, which were composed of the hydrophilic block (A) and the hydrophobic helical block (B) but with a different helix sense between the two host polypeptides. TEM and DLS revealed the formation of vesicles with ca. 100 nm diameter. The molecular assembly was driven by hydrophobic interaction, stereocomplex formation, and dipole–dipole interaction between hydrophobic helices. Furthermore, the A₃B-type host polypeptide extended the hydrophilic block to the outer surface of vesicles as a result of the steric effect, resulting in the formation of unsymmetrical vesicular membranes. As a result, a functionalized AB-type guest polypeptide having the same helix sense with the A₃B-type host polypeptide exposed the hydrophilic block to the outer surface. In contrast, an AB-type guest polypeptide having the same helix sense with the AB-type host polypeptide oriented the hydrophilic block to the inner surface. Functionalization of either the outer or inner surface of the binary vesicle is therefore facile to achieve when using either the right- or the left-handed helix of the functionalized guest polypeptide

Morphology Control between Twisted Ribbon, Helical Ribbon, and Nanotube Self-Assemblies with His-Containing Helical Peptides in Response to pH Change

pH-Responsive molecular assemblies with a variation in morphology ranging from a twisted ribbon, a helical ribbon, to a nanotube were prepared from a novel A₃B-type amphiphilic peptide having three hydrophilic poly­(sarcosine) (A block) chains, a hydrophobic helical dodecapeptide (B block), and two histidine (His) residues between the A₃ and B blocks. The A₃B-type peptide adopted morphologies of the twisted ribbon at pH 3.0, the helical ribbon at pH 5.0, and the nanotube at pH 7.4, depending upon the protonation states of the two His residues. On the other hand, another A₃B-type peptide having one His residue between the A₃ and B blocks showed a morphology change only between the helical ribbon and the relatively planar sheets with pH variation in this range. The morphology change is thus induced by one- or two-charge generation at the linking site of the hydrophilic and hydrophobic blocks of the component amphiphiles but in different ways

Self-Assemblies of Triskelion A₂B-Type Amphiphilic Polypeptide Showing pH-Responsive Morphology Transformation

A pH-responsive rolled-sheet morphology was prepared from a triskelion A₂B-type amphiphilic polypeptide having a histidine residue as a pH-responsive unit. The dimensions of the rolled sheet were 85 nm diameter and 210 nm length with a sheet turn number of 2.0 at pH 7.4. Upon decreasing the pH from 7.4 to 5.0, the layer spacing of the rolled sheets was widened from ca. 9 to ca. 19 nm due to electrostatic repulsion caused by histidine protonation. This morphology change occurred reversibly with a pH change between 7.4 and 5.0. The molecular packing in the rolled sheets was shown to be loosened at pH 5.0 on the basis of electron diffraction measurements. The tightness of the rolled sheets was thus controlled reversibly by a pH change due to a single protonation in the amphiphilic polypeptide