Heteromultivalent recognition originated from the "marriage" of cyclodextrin and calixarene amphiphiles

Published in Chemistry
Heteromultivalent recognition originated from the "marriage" of cyclodextrin and calixarene amphiphiles
Like

Share this post

Choose a social network to share with, or copy the URL to share elsewhere

This is a representation of how your post may appear on social media. The actual post will vary between social networks

Multivalent interactions are vital in biological process. Heteromultivalency is very common in proteins and membranes that typically interact with heterotopic contact surfaces. For binding ligands with multiple different kinds of sites, heteromultivalency is necessary to achieve sufficient affinity and high specificity at the same time. Currently, a most suitable model of biological receptors are macrocyclic hosts, displaying complementary binding to certain guests. However, realizing artificial heteromultivalency by covalent methods is a formidable challenge because of intensive and time-consuming synthesis. Moreover, it is very difficult to precisely control the spatial arrangement of binding sites in diverse macrocycles to match the ligand sequence and/or dynamics at structurally complex biointerfaces.

The Ravoo group in Münster has focused on amphiphilic cyclodextrin (CD) for a long time, while the Guo group at Nankai University has explored amphiphilic calixarene (CA). In November 2014, Prof. Guo visited Prof. Ravoo in Münster. We had a very nice discussion, and envisaged that the “marriage” between CA and CD could be a powerful combination. CD and CA are two kinds of macrocyclic receptors with orthogonal binding sites. As a result, co-assembling CD and CA amphiphiles (“marriage”) would give rise to the self-assembled heteromultivalency. This was the beginning of our collaborative project. To make the collaboration run smoothly, in Jan. 2016, Prof. Guo sent Dr. Xu to Prof. Ravoo’s group as an exchange student for one year. By employing various tyrosine- and lysine-rich model peptides, Dr. Xu demonstrated the heteromultivalent recognition that we had anticipated. Moreover, the CD−CA dynamic co-assembly is self-adaptive, enable a self-optimization to obtain an optimal spatial arrangement of the binding sites. 

The “marriage” is interesting, but so what? What special applications can be realized? Eventually, as a proof-of-concept application of the artificial heteromultivalency constructed, together with Prof. Yuan and Wang at Nankai University, we successfully used the CD−CA co-assembly to inhibit amyloid-β peptide fibrillation, dissolving fibrils and reducing amyloid cytotoxicity. The fibrillation of amyloid-β peptides is the hallmark of Alzheimer’s disease, so our work may inspire new strategies for the treatment of Alzheimer’s disease, although we are aware that at present it is not certain whether amyloid deposits are the cause or a consequence of Alzheimer´s disease.

All the details of our work can be read in our article: “Heteromultivalent Peptide Recognition by Co-Assembly of Cyclodextrin and Calixarene Amphiphiles Enables Inhibition of Amyloid Fibrillation” in Nature Chemistry.

Please sign in or register for FREE

If you are a registered user on Research Communities by Springer Nature, please sign in

Follow the Topic

Chemistry
Physical Sciences > Chemistry
  • Nature Chemistry Nature Chemistry

    A monthly journal dedicated to publishing high-quality papers that describe the most significant and cutting-edge research in all areas of chemistry, reflecting the traditional core subjects of analytical, inorganic, organic and physical chemistry.