Amyloid, which is formed by fibrillation of proteins, has been reported to relate to numbers of diseases, such as Alzheimer's disease, Parkinson's disease, and type II diabetes. Therefore, inhibiting the amyloidosis of proteins is of great significant in terms of prevention and therapy of related diseases. One core issue of inhibiting protein fibrillation is based on the molecular recognition, which needs the designed receptors to afford high binding affinity and specificity to pathogenic target proteins. Our interest is inhibiting amyloid fibrillation via host-guest interactions. We designed novel macrocyclic amphiphiles, which co-assemble into the heteromultivalent recognition platform. The heteromultivalent recognition makes co-assemblies selectively and strongly bind to the target proteins, and then inhibit and dissolve their fibrillation efficiently. The co-assembled heteromultivalency paves an avenue for the prevention and treatment of amyloid fibrillation related diseases.

Recently, our group developed a novel heteromultivalent platform by co-assembling cyclodextrin and calixarene amphiphiles that shows strong and selective binding towards tyrosine- and lysine-rich peptides. The dynamic feature of self-assembly endows the platform with self-adaptability to better match the biologically relevant heterotopic species with complex ligand sequences. The co-assembly achieved nanomolar binding to Alzheimer's disease-related Aβ-peptide (Aβ₄₂), and was successfully engaged in inhibiting Aβ₄₂ fibrillation as well as dissolving Aβ₄₂ fibrils. Cell experiments demonstrated that the co-assembly had good biocompatibility and was able to protect neuronal cells from Aβ₄₂-induced cytotoxicity. This self-assembled heteromultivalency concept is easily amenable to other ensembles and targets, so that versatile biomedical applications can be envisaged. (Nat. Chem., 2019, 11, 86-93, collaborated with Prof. Bart Jan Ravoo)