Nanomorphological Diversity of Self-Assembled Cyclopeptisomes Investigated via Thermodynamic and Kinetic Controls

Abstract

The physicochemical and biological characteristics of vesicles are dependent on the type of self-assembly building blocks and methods of preparation. In this report, we designed a vesicle-forming linear and cyclic peptide building blocks and investigated the effect of molecular topology and thermodynamic and kinetic controls on the stability and morphological features of the self-assembled vesicles. Comparison of topological effect on self-assembly revealed that the strong association of the aromatic hydrophobic segments is observed only in the cyclic peptide, which is most likely the results of constrained structure along with the restriction in the molecular degree of freedom. Consequently, the formation of stable vesicles could be observed only with the cyclic peptide. Further investigation with cyclic peptide building blocks revealed that depending on the control methods, vesicles with a variety of structural features, such as polygonal, wrinkled, round, round-patched, and round-fused vesicles, could be fabricated. Our results demonstrate that existing vesicle structures constitute only a fraction of the possible structural diversity and that macrocyclic peptides can provide a wealth of opportunities in vesicle engineering.

Protonation-Induced Self-Assembly of Flexible Macrocyclic Diacetylene for Constructing Stimuli-Responsive Polydiacetylene

“…Macrocycles are appealing chemical structures that offer a shape-persistent self-assembly. Macrocyclic molecular frame controls the self-assembly pattern and is thus considered a straightforward and versatile approach for the creation of regulated predefined morphology. − The macrocyclic structure features a confined cavity and self-stacks into the unidirectional columnar assembly for generating highly organized hollow tubular nanochannels. , Since the columnar assembly of macrocycles mainly relies on sequential noncovalent interactions, these structures lack stability upon exposure to unfavorable environment conditions. Accordingly, they are likely to lose tubular morphology due to weakening or collapse in noncovalent interactions.…”

Self‐assembling cyclic peptide‐oligonucleotide conjugates: Synthetic strategies and the effect of cyclic topology on self‐assembly and base pairing

“…The overall CD spectra of both LinPOC-1 and CycPOC-1 showed similar patterns, with the minima being slightly different ( Figure 3A, 204 nm for LinPOC-1 and 202 nm for CycPOC-1), which is consistent with the slight discrepancy in retention times observed by HPLC. Since cyclization often causes a change in the peptide conformation, [30][31] we further inves- and C-duplex (CycPOC-1/CycPOC-2). Since the CD spectrum of DNA is quite sensitive to its conformation [32] and DNA duplex can be unwound as the temperature increases, we speculated that a change in CD values with the temperature would reflect the extent of DNA whereas that of a partially formed DNA duplex would not change as much as that of a fully formed DNA duplex.…”

“…The overall CD spectra of both LinPOC‐1 and CycPOC‐1 showed similar patterns, with the minima being slightly different (Figure 3A, 204 nm for LinPOC‐1 and 202 nm for CycPOC‐1 ), which is consistent with the slight discrepancy in retention times observed by HPLC. Since cyclization often causes a change in the peptide conformation, [ 30–31 ] we further investigated whether cyclization affected the conformation of the peptide in POCs by subtracting the DNA‐1 spectrum from the spectra of LinPOC‐1 and CycPOC‐1 , and the resulting spectra were compared with that of Pep‐1 (Figure 3B). It turned out that the peptide parts in both conjugates were in random coil conformation, suggesting that the cyclization did not have a significant effect on the peptide conformation of the POCs.…”

3D2 Self‐Assembling Janus Peptide Dendrimers with Tailorable Supermultivalency

“…For example, some of the most widely studied peptide amphiphiles and other linear self‐assembling peptides are characterized by having a 1D hydrophilic segment and a 1D self‐assembling segment (1D × 1D). Cyclic peptide building blocks incorporate both of the segments in a 2D plane (2D × 2D) . There are examples of peptide building blocks containing hydrophobic dendrimer segments (3D), but their hydrophilic peptide segments were still 1D (1D × 3D) .…”