Co-assembly of helical β³-peptides: a self-assembled analogue of a statistical copolymer

Abstract

Unnatural peptide self-assembly offers the means to design hierarchical nanostructures of controlled geometries, chemical function and physical properties. N-acyl β 3 peptides, where all residues are unnatural amino acids, are able to form helical fibrous structures by a head-to-tail assembly of helical monomers, extending the helix via a three point supramolecular hydrogen bonding motif. These helical nanorods were shown to be stable under a wide range of physical conditions, offering a self-assembled analogue of polymeric fibres. Hitherto the self-assembly has only been demonstrated between identical monomers; however the self-assembly motif is sequence-independent, offering the possibility of hetero-assembly of different peptide monomers. Here we present a proof of principle study of head-to-tail co-assembly of two different helical unnatural peptides Ac-β [LIA], where the letters denote the β 3 analogues of natural amino acids. By atomic force microscopy imaging it was demonstrated that the homo-assembly and co-assembly of these peptides yield characteristically different structures. Synchrotron small angle X-ray scattering experiments have confirmed the presence of the fibres in the solution and the averaged diameters from modelled data correlate well to the results of AFM imaging. Hence, there is evidence of co-assembly of the fibrous superstructures; given that different monomers may be used to introduce variations into chemical and physical properties, the results demonstrate a self-assembled analogue of a statistical co-polymer that can be used in designing complex functional nanomaterials.

A two-dimensional metallosupramolecular framework design based on coordination crosslinking of helical oligoamide nanorods

“…The supramolecular three point hydrogen bonding motif that yields the head-to-tail self-assembly of helical b 3 -oligoamide units is very strong, hence fibres are observed in water and even in DMSO, 25 without a noticeable monomeric/small oligomeric population. 26,27 For this reason, traditional characterization methods such as NMR or CD are not feasible to perform, and therefore structure can only be inferred from microscopy imaging and indirect characterization methods.…”

Coordination crosslinking of helical substituted oligoamide nanorods with Cu(II)

“…[20][21][22] One dimensional assembly of the 14-helices can be achieved by the acylation of the N-terminus of the oligoamides, yielding a head-to-tail 3-point hydrogen-bonding motif that copies the intramolecular 14-helix hydrogen bonding pattern to the termini. [1,[17][18][19][23][24][25] The resulting nanorods are stable in a range of solvents and may also assemble into a wide variety of superstructures, such as fibrils, rope-like bundles, dendritic, and mesh-like structures. [17][18][19][23][24][25] These superstructures form through a variety of interactions including hydrophobic attractions, van der Waals interactions, and supramolecular H-bonding interactions, the strength and propensity of which are strongly dependent on the oligoamide primary structure (i.e.…”

“…[1,[17][18][19][23][24][25] The resulting nanorods are stable in a range of solvents and may also assemble into a wide variety of superstructures, such as fibrils, rope-like bundles, dendritic, and mesh-like structures. [17][18][19][23][24][25] These superstructures form through a variety of interactions including hydrophobic attractions, van der Waals interactions, and supramolecular H-bonding interactions, the strength and propensity of which are strongly dependent on the oligoamide primary structure (i.e. side chains and cross section geometry), as well as the chemical and physical properties of the solvents used.…”

“…side chains and cross section geometry), as well as the chemical and physical properties of the solvents used. [17][18][19][23][24][25] The diversity of superstructures available from oligoamides coupled with the high level of control achievable via molecule design and assembly conditions makes substituted oligoamides remarkably robust candidates for the design of spontaneously assembling nano-materials. [1,9,[17][18][19][23][24][25] In particular, the stability of the 14-helix raises the possibility of using metal coordination to crosslink the supramolecular nanorod assemblies without interfering with the primary supramolecular assembly motif; yielding a hitherto unprecedented metallosupramolecular framework (MSF) structure.…”

“…Atomic Force Microscopy (AFM) can confirm the existence of the nanorod assembly and image the superstructure of deposits, while small angle scattering methods can provide the same information for suspensions. [25] Both SANS (small angle neutron scattering) and SAXS (small angle X-ray scattering) can be used to obtain the morphological envelope of molecules but with marked differences. In SAXS the X-ray beam interacts with electron densities of heavier elements, hence more sensitive to revealing core structure.…”