Heteromultivalency, which involves the simultaneous interactions of more than one type of ligand with more than one type of receptor, is ubiquitous in living systems and provides a powerful strategy to improve the binding efficiency of heterotopic species such as proteins and membranes. However, the design and development of artificial heteromultivalent receptors is still challenging owing to tedious synthesis processes and the need for precise control over the spatial arrangement of the binding sites. Here, we have designed a heteromultivalent platform by co-assembling cyclodextrin and calixarene amphiphiles, so that two orthogonal, non-covalent binding sites are distributed on the surface of the co-assembly. Binding with model peptides shows a synergistic effect of the two receptors, (hetero)multivalency and self-adaptability. The co-assembly shows promise for inhibition of the fibrillation of amyloid-β peptides and the dissolution of amyloid-β fibrils, substantially reducing amyloid cytotoxicity. This self-assembled heteromultivalency concept is easily amenable to other ensembles and targets, so that versatile biomedical applications can be envisaged.
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The data supporting the findings of this study are available within the paper and its Supplementary Information, and from the corresponding author upon reasonable request.
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The Chinese team acknowledges support from the NNSFC (21672112 and 51873090), Fundamental Research Funds for the Central Universities and the Program of Tianjin Young Talents. The German team thanks T. Böckerman for the synthesis of amphiphilic CD and the Deutsche Forschungsgemeinschaft (DFG SFB 858) for financial support.
The authors declare no competing interests.
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Xu, Z., Jia, S., Wang, W. et al. Heteromultivalent peptide recognition by co-assembly of cyclodextrin and calixarene amphiphiles enables inhibition of amyloid fibrillation. Nature Chem 11, 86–93 (2019). https://doi.org/10.1038/s41557-018-0164-y
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