Self-assembling peptides have the ability to spontaneously aggregate into large ordered structures. The reversibility of the peptide hydrogen bonded supramolecular assembly make them tunable to a host of different applications, although it leaves them highly dynamic and prone to disassembly at the low concentration needed for biological applications. Here we demonstrate that a secondary hydrophobic interaction, near the peptide core, can stabilise the highly dynamic peptide bonds, without losing the vital solubility of the systems in aqueous conditions. This hierarchical self-assembly process can be used to stabilise a range of different β-sheet hydrogen bonded architectures.
Self-assembling cyclic peptide-polymer nanotubes have emerged as a fascinating supramolecular system, well suited for a diverse range of biomedical applications. Due to their well-defined diameter, tunable peptide anatomy, and ability to disassemble in situ, they have been investigated as promising materials for numerous applications including biosensors, antimicrobials, and drug delivery. Despite this continuous effort, the underlying mechanisms of assembly and disassembly are still not fully understood. In particular, the exchange of units between individual assembled nanotubes has been overlooked so far, despite its knowledge being essential for understanding their behavior in different environments. To investigate the dynamic nature of these systems, cyclic peptide-polymer nanotubes are synthesized, conjugated with complementary dyes, which undergo a Förster resonance energy transfer (FRET) in close proximity. Model conjugates enable to demonstrate not only that their self-assembly is highly dynamic and not kinetically trapped, but also that the self-assembly of the conjugates is strongly influenced by both solvent and concentration. Additionally, the versatility of the FRET system allows studying the dynamic exchange of these systems in mammalian cells in vitro using confocal microscopy, demonstrating the exchange of subunits between assembled nanotubes in the highly complex environment of a cell. Nanotubes
This Review focuses on the establishment
and development of self-assemblies
governed by the supramolecular interactions between cyclic peptides.
The Review first describes the type of cyclic peptides able to assemble
into tubular structures to form supramolecular cyclic peptide nanotubes.
A range of cyclic peptides have been identified to have such properties,
including α-peptides, β-peptides, α,γ-peptides,
and peptides based on δ- and ε-amino acids. The Review
covers the design and functionalization of these cyclic peptides and
expands to a recent advance in the design and application of these
materials through their conjugation to polymer chains to generate
cyclic peptide–polymer conjugates nanostructures. The Review,
then, concentrates on the challenges in characterizing these systems
and presents an overview of the various analytical and characterization
techniques used to date. This overview concludes with a critical survey
of the various applications of the nanomaterials obtained from supramolecular
cyclic peptide nanotubes, with a focus on biological and medical applications,
ranging from ion channels and membrane insertion to antibacterial
materials, anticancer drug delivery, gene delivery, and antiviral
applications.
Typically, the morphologies of the self-assembled nanostructures from block copolymers are limited to spherical micelles, wormlike micelles and vesicles. Now, a new generation of materials with unique shape and structures, cylindrical soft matter particles (tubisomes), are obtained from the hierarchical self-assembly of cyclic peptide-bridged amphiphilic diblock copolymers. The capacity of obtained photoresponsive tubisomes as potential drug carriers is evaluated. The supramolecular tubisomes pave an alternative way for fabricating polymeric tubular structures, and will expand the toolbox for the rational design of functional hierarchical nanostructures.
Self-assembling cyclic peptides (CP) consisting of amino acids with alternating d- and l-chirality form nanotubes by hydrogen bonding, hydrophobic interactions, and π-π stacking in solution. These highly dynamic materials are emerging as promising supramolecular systems for a wide range of biomedical applications. Herein, we discuss how varying the polymer conformation (linear vs. brush), as well as the number of polymer arms per peptide unimer affects the self-assembly of PEGylated cyclic peptides in different solvents, using small angle neutron scattering. Using the derived information, strong correlations were drawn between the size of the aggregates, solvent polarity, and its ability to compete for hydrogen bonding interactions between the peptide unimers. Using these data, it could be possible to engineer cyclic peptide nanotubes of a controlled length.
Breaking away from the linear structure of previously reported peptide‐based gelators, this study reports the first example of gel formation based on the use of cyclic peptides made of alternating d‐ and l‐amino acids, known to self‐assemble in solution to form long nanotubes. Herein, a library of cyclic peptides was systemically studied for their gelation properties in various solvents, uncovering key parameters driving both organogel and hydrogel formation. The hierarchical nature of the self‐assembly process in water was characterised by a combination of electron microscopy imaging and small‐angle X‐ray scattering, revealing a porous network of entangled nanofibres composed by the aggregation of several cyclic peptide nanotubes. Rheology measurements then confirmed the formation of soft hydrogels.
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