Search

We have designed and synthesized two α-helicomimetic foldamers composed of six urea residues with terminal ferrocene and cysteamine moieties. The direction of the net dipole moment in these two com...

We report here an oligourea foldamer able to self-assemble in aqueous conditions into helix bundles of multiple stoichiometries. Importantly, we report crystal structures of several of these stoichiometries, providing a series of high-resolutions snap-shots of the structural polymorphism of this foldamer and uncovering a novel self-assembly.

α-Helicomimetic oligoureas are a class of compounds with a broad spectrum of applications, yet their use in materials science remains still unexplored. In this work, we have synthesized three oligomers composed of 8–12 residues and studied their electron transport characteristic. We have found that the conductance of oligoureas depends on the length of the molecule. The distance dependence yields a low value of the decay constant, which indicates that the dominant mechanism is hopping. Moreover, we describe here an entirely new property of oligoureas, that is, directional dependence of electron transport. The latter is manifested on current–voltage characteristic as current rectification. The highest rectification ratio observed was ≈12, which is around 3 times greater than that observed for helical peptides of similar length. This effect demonstrates that carefully designed oligomers with a well-defined secondary structure (e.g., oligourea foldamers) may be considered as potential candidates for use in n...

Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies.

International audience; The synthesis of hybrid urea-based foldamers containing isosteric guanidinium linkages at selected positions in the sequence is described. We used a postelongation approach whereby the guanidinium moiety is introduced by direct transformation of a parent oligo(urea/thiourea) foldamer precursor. The method involves activation of the thiourea by treatment with methyl iodide and subsequent reaction with amines. To avoid undesired cyclization with the preceding urea moiety, resulting in heterocyclic guanidinium formation in the main chain, the urea unit preceding the thiourea unit in the sequence was replaced by an isoatomic and isostructural gamma-amino acid. The approach was extended to solid-phase techniques to accelerate the synthesis of longer and more functionalized sequences. Under optimized conditions, an octamer hybrid oligomer incorporating a central guanidinium linkage was obtained in good overall yield and purity. This work also reports data related to the structural consequences of urea by guanidinium replacements in solution and reveals that helical folding is substantially reduced in oligomers containing a guanidinium group.

Common surfactants promote the crystallisation of a series of water-soluble oligourea foldamers which had previously proven resistant to crystallisation efforts., X-ray crystallography has played a major role in the advancement of foldamer research, however, obtaining well-formed single crystals of suitable quality for structure determination by X-ray diffraction methods is often rather challenging. Towards this end, we report here the ability of common surfactants to promote the crystallisation of a series of water-soluble oligourea foldamers which had previously proven highly resistant to crystallisation. Four high-resolution crystal structures are reported, suggesting certain surfactants could be potentially useful tools for the crystallisation of intractable water-soluble foldamers (or peptides).

We report here the efficient in situ iodination of tyrosine-type side-chains located within a foldamer helix bundle, permitting structure determination using single-wavelength anomalous diffraction (SAD) methods. We suggest that this simple method may be of use to those engaged in structural foldamer research as a potential solution to the phase problem.

Working with thiols is associated with the risk of unwanted oxidation reactions, which includes the formation of disulfides. Here, the use of short peptidomimetic oligoureas as a model system to study the influence of reaction conditions on the thiol oxidation process is described. The formation of disulfide bond is usually performed in aqueous solutions; in this study, it was shown that the oxidation reaction occurs also in organic medium. It was discovered that the rate of the oxidation reaction strongly depends on the type of solvent, which is the consequence of the change of the oxidant (air or DMSO), the temperature, and the presence (or absence) of base. The details reported here may help those working with thiols to find suitable conditions to control the oxidation behaviour in organic solvents, ensuring that ─SH groups either remain intact or form disulfide bonds as desired.