In this work, we present the combination of supramolecular structures and dendritic functionalisation with a view to multivalent ligand-receptor recognition. To this end, we studied two supramolecular systems, i.e., 1,3,5-benzenetricarboxamide (BTA)-based one-dimensional polymers and spherical β-cyclodextrin-based vesicles.
We could show that dendronised BTA-C16-G1 molecules, functionalised with dendritic polyglycerol head groups, assemble in water in stable one-dimensional polymers with a high aspect ratio. HDX experiments showed remarkable low exchange dynamics of the monomers within the polymer. By cryo-TEM and subsequent image processing, an intriguing ultrastructure, consisting of two adjacent fibre strands, was revealed for the fibrous aggregates. Moreover, a double-helix ultrastructure was elucidated for ethylene-glycol functionalised nBTA polymers, comprising linear side chains.
Intriguingly, the length of the double-helix pitch could be varied by copolymer formation as a
function of the monomer ratio. Starting from nBTA polymers, the pitch length was increased
with an increasing amount of BTA-C16-G1, which can be interpreted as unwinding of the
double-helix towards the presence of two parallel strains. At the same time, the monomer
exchange dynamics of nBTA were lowered upon copolymer formation with BTA-C16-G1.
Contrarily, the helix pitch of nBTA polymers was decreased upon copolymer formation with
BTA-C12-G1, leading to a higher axial curvature of the polymer strands. BTA-C12-G1 itself
assembles in spherical micelles, hence, a morphology with a high spatial curvature. However,
also here, the monomer exchange dynamics of nBTA were lowered in copolymers with
BTA-C12-G1, underlining a stabilisation effect induced by the dendritic head groups. These
results contribute to the understanding of the interplay between structure and dynamics of
supramolecular polymers, which is of fundamental interest when designing functional materials.
Multivalent carbohydrate-recognition processes are omnipresent in nature, for instance, between the cell surface and pathogens during infection processes. Glyco-functionalised supramolecular architectures are promising functional materials for the interaction and inhibition of multivalent biological receptors due to their adaptivity based on reversible interactions and variable copolymer formation. Aiming for one-dimensional functional architectures, we studied two mannose-functionalised BTAs with and without an ethyleneglycol (EG) spacer, regarding their assembly into supramolecular polymers and their ability to efficiently bind to mannose-binding lectins. BTA-mannose was shown to assemble into a fibre structure, whereas the BTA-EG4-mannose formed spherical micelles instead. However, copolymer formation with non-glycosylated nBTA resulted in the assembly of fibres and made it possible to adjust the carbohydrate concentration within the polymer. We could show that multivalent copolymers of BTA-EG4-mannose and nBTA were able to bind to mannose-binding lectin (complement assay) and concanavalin A (ConA) (turbidity assay) with KD values up to the low micromolar range for the latter case. Our results obtained from lectin binding studies with two different mannose-binding proteins underline that for the design of efficient binders, structural knowledge of both the binder and the receptor structure is crucial. As a perspective, the combination of dendronised BTAs with carbohydrate functionalisation is believed to result in potent multivalent biofunctional materials.
Based on β-cyclodextrin vesicles (CDVs), a supramolecular toolbox approach for multivalent
ligand-receptor recognition was established. A series of bifunctional ligands for CDVs
was synthesised. These ligands comprise on one side adamantane, enabling the functionalisation of CDVs with these ligands, and either mannose or sulphate group moieties on the other side for biological receptor recognition. The physicochemical properties of the hostguest complexes formed by β-cyclodextrin and adamantane were determined by isothermal titration calorimetry (ITC). Ligand-lectin interactions were investigated by surface plasmon resonance experiments (SPR) for the mannose ligands and ConA. Microscale thermophoresis (MST) measurements were applied for sulphate-dependent binding to l-selectin. In both cases, a multivalent affinity enhancement became apparent when the ligands were presented on the CDV scaffold. Furthermore, not only the clustering between our supramolecular mannosylated complex and Escherichia coli (E. coli) expressing the lectin FimH was visualised by cryo-TEM, but also the competitive character to detach bound E. coli from a cell line representing the uroepithelial cell surface was demonstrated. Thus, a facile and effective supramolecular toolbox was established for various ligand-receptor recognition applications.