New supramolecular Alzheimer’s drugs

Supramolecular chemistry could provide a new avenue in the treatment of Alzheimer’s disease, say scientists in China. The group demonstrates for the first time that supramolecular complexes can inhibit the aggregation of a peptide thought to cause Alzheimer’s disease.

Alzheimer’s disease (AD) is the most common cause of dementia among the elderly and is estimated to affect over 35 million people worldwide, a figure which is expected to triple by 2050. One of the pathological hallmarks of the disease is the polymerisation of amyloid β-peptides (Aβ) into insoluble fibrous protein aggregates known as plaques. Scientists have been trying to develop inhibitors of Aβ aggregation as a therapeutic and preventive strategy for AD treatment. Most reported Aβ inhibitors are small organic molecules or peptides, many of which act non-specifically.

Xiaogang Qu and coworkers at the Changchun Institute of Applied Chemistry used a novel cell-based screening system, which relies on tagging Aβ with a slow-folding fluorescent protein, to identify two metallo-supramolecular ‘cylinders’ that are able to inhibit Aβ aggregation by targeting the central region of the peptide. These cylinders were found to resemble so-called zinc fingers, small protein structural motifs that typically bind one or more zinc ions and impart versatile binding to other proteins or DNA.

In addition, the complexes were found to destabilise pre-formed Aβ plaques. ‘The inhibition effect is significant for preventing the development of AD symptoms at an early stage, while the destabilisation effect is of great benefit for reversing the progression of AD,’ says Qu.

‘Supramolecular chemistry has provided many outstanding insights into biological systems, so it is exciting to see this rich field expanded to include the areas of Aβ aggregation and Alzheimer’s disease,’ remarks Zachary Mensinger at the Institute for Neurodegenerative Diseases, University of California, San Francisco, US.

In vivo studies in mice revealed that the complexes are capable of decreasing the level of insoluble Aβ and alleviating spatial memory deficits, although Tim Storr at Simon Fraser University, Canada, notes that ‘it remains to be determined whether these cationic complexes cross the blood–brain barrier or are acting systemically’.




  1. H Yu et al, Chem. Sci., 2012, DOI: 10.1039/c2sc20372c

Related Content

Breaking the mould with recycled plastic drugs

10 December 2013 Research

news image

Supramolecular anti-fungal drug made from old PET bottles could help tackle resistance problems

Drug fix for misfolded proteins promises hope for incurable diseases

9 December 2013 Research

news image

Small molecules could target proteins involved in Alzheimer's disease and cystic fibrosis

Most Commented

How to print a crystal in 3D

17 April 2014 Research

news image

Rather than looking at a crystal on a screen, print it out and hold it in your hand

Graphene made in a kitchen blender

22 April 2014 Research

news image

High quality flakes of two-dimensional material exfoliated from graphite points way to bulk production