Transition of Nano-Architectures Through Self-Assembly of Lipidated β3-Tripeptide Foldamers

Abstract

β 3-peptides consisting exclusively of β 3-amino acids adopt a variety of non-natural helical structures and can self-assemble into well-defined hierarchical structures by axial head-to-tail self-assembly resulting in fibrous materials of varying sizes and shapes. To allow control of fiber morphology, a lipid moiety was introduced within a tri-β 3-peptide sequence at each of the three amino acid positions and the N-terminus to gain finer control over the lateral assembly of fibers. Depending on the position of the lipid, the self-assembled structures formed either twisted ribbon-like fibers or distinctive multilaminar nanobelts. The nanobelt structures were comprised of multiple layers of peptide fibrils as revealed by puncturing the surface of the nanobelts with an AFM probe. This stacking phenomenon was completely inhibited through changes in pH, indicating that the layer stacking was mediated by electrostatic interactions. Thus, the present study is the first to show controlled self-assembly of these fibrous structures, which is governed by the location of the acyl chain in combination with the 3-point H-bonding motif. Overall, the results demonstrate that the nanostructures formed by the β 3-tripeptide foldamers can be tuned via sequential lipidation of N-acetyl β 3-tripeptides which control the lateral interactions between peptide fibrils and provide defined structures with a greater homogeneous population.

Self-Assembling Hydrogel Structures for Neural Tissue Repair

“…The nanotopography of self-assembled structures can be modulated by varying the molecular structure or the environment in which the self-assembly occurs. More specifically, techniques such as changing the molecular design, electrostatic capping, pH, self-assembly molecule concentration or solvents have all been used to control the formation of micelles, β-sheets, α-helix, nanobelts, and membranes. − Figure illustrates various structures formed under different conditions. For example, Ghosh et al developed a PA that would transition from molecules dispersed in solution to micelles or nanofibers based on pH.…”

Staphylococcus aureus entanglement in self-assembling β-peptide nanofibres decorated with vancomycin

“…20,23 More recently, we demonstrated the controlled self-assembly of lipidated N-acetyl b 3 -peptides to give a range of well-dened bres and nano-ribbons. 28 Also, these materials can form biocompatible hydrogels for cell culture [29][30][31][32] and in vivo applications. 33,34 The activity of these b 3 -peptide materials has been modulated through the introduction of novel b-amino acids containing cell adhesion epitopes and uorophores for localisation studies.…”

“…This strategy could be further exploited by incorporating modular functionalities into the b 3peptide bre, which would allow extracellular traps to be decorated with enzymes displaying antimicrobial activities. Since lipidated b-peptides are also able to form hydrogels, 28,30,32 the potential of these peptides to yield antimicrobial hydrogels would have wide application in areas such as wound management. Moreover, b 3 -peptide materials could provide a scaffold within the wound allowing migration of cells into the gel 34 while also inhibiting bacterial growth, which are two important properties for the treatment of chronic wounds.…”

Supramolecular Self‐Assembly of β3‐Peptides Mediated by Janus‐Type Recognition Units

“…[6,9,10] By functionalizing the flanks of a1 4-helix with recognition units at ad istance of i and i + 3, the side chains of the insertedu nits are aligned with a stacking distance of 5 .T he control over geometry,s toichiometry and specificity of self-association can be increased by using specific recognition units. [11] In previous work we could show assemblies basedo nt he 14-helical structure of b 3 -peptides, using canonicaln ucleobases as recognition units. [12] Complementary nucleobase-functionalized b-peptidesc ould form stableh elix dimers by Watson-Crick and Hoogsteen base pairing.…”

“…The control over geometry, stoichiometry and specificity of self-association can be increased by using specific recognition units. [11] In previous work we could show assemblies based on the 14-helical structure of b 3 -peptides, using canonical nucleobases as recognition units. [12] Complementary nucleobase-functionalized b-peptides could form stable helix dimers by Watson-Crick and Hoogsteen base pairing.…”