ADVERTISEMENT
2 /3 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.

If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.

ENJOY UNLIMITED ACCES TO C&EN

Biological Chemistry

Polymer-Peptide Conjugate Redirects Amyloid Fibril Growth

Self-Assembly: Researchers design a macromolecule that causes amyloid-β peptide to assemble into discrete nanostructures instead of fibrils

by Laura Cassiday
April 10, 2014

Fibrils, Interrupted
20140410lnj1-040714Abeta.jpg
Credit: J. Am. Chem. Soc.
In the presence of a polymer–peptide conjugate (right, gray and red), amyloid-β (Aβ) peptides form nearly spherical nanostructures (micrograph), rather than the fibrils (left) associated with Alzheimer’s disease.

In the brains of people with Alzheimer’s disease, amyloid-β (Aβ) peptides assemble into fibrils, which in turn tangle together to form amyloid plaques. In a new study, chemists designed macromolecules that redirect Aβ’s aggregation from microscale fibrils to nearly spherical nanostructures (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja501102f). The findings could help illuminate how amyloid fibrils grow, as well as suggest new therapeutic strategies for the disease, the researchers say.

Amyloid fibril growth has two stages: a slow nucleation phase characterized by weak interactions between Aβ monomers, and an elongation phase in which the amyloid chain grows rapidly. Jeffrey S. Moore and his colleagues at the University of Illinois, Urbana-Champaign reasoned that by interfering with the nucleation phase, they could perhaps disrupt amyloid assembly. So they synthesized inhibitor molecules that contained multiple copies of an Aβ-binding peptide attached to a linear copolymer backbone. The peptide they used binds to a specific region of Aβ that interacts with other Aβ monomers.

The team found that when a polymer-peptide conjugate containing 21 copies of the Aβ-binding peptide was added to an equal amount of Aβ peptide, the conjugate completely suppressed fibril formation. But, at an equivalent concentration, the binding peptide alone did not affect how Aβ assembled. The researchers found that in the presence of the polymer-peptide conjugate, Aβ formed nearly spherical structures about 30 nm in diameter, which surprised the chemists.

“We were trying to inhibit fibrillar growth,” says Moore. “The reproducible appearance of nanostructures of discrete size and shape was completely unexpected.” The researchers are currently investigating the composition of these nanostructures. Understanding the structures and how they form may suggest new ways to prevent or disrupt amyloid aggregation, Moore says.

Advertisement
X

Article:

This article has been sent to the following recipient:

Leave A Comment

*Required to comment