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Nat Chem. 2019 Jan;11(1):86-93. doi: 10.1038/s41557-018-0164-y. Epub 2018 Nov 19.

Heteromultivalent peptide recognition by co-assembly of cyclodextrin and calixarene amphiphiles enables inhibition of amyloid fibrillation.

Author information

1
College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials, Ministry of Education, Nankai University, Tianjin, China.
2
Organic Chemistry Institute and Center for Soft Nanoscience (SoN), Westfälische Wilhelms-Universität Münster, Münster, Germany.
3
College of Life Sciences, Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China.
4
Organic Chemistry Institute and Center for Soft Nanoscience (SoN), Westfälische Wilhelms-Universität Münster, Münster, Germany. b.j.ravoo@uni-muenster.de.
5
College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials, Ministry of Education, Nankai University, Tianjin, China. dshguo@nankai.edu.cn.
6
Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin, China. dshguo@nankai.edu.cn.

Abstract

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.

PMID:
30455432
DOI:
10.1038/s41557-018-0164-y
[Indexed for MEDLINE]

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