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Rotello group uses gold nanoparticles to restore structure, function to misfolded proteins

Proteins are masters of origami, folding into complex shapes that allow them to perform a specific job in living cells. When proteins become misfolded, however, they lose their function. Chemistry professor Vincent Rotello and graduate student Mrinmoy De have shown that gold nanoparticles can restore much of the lost structure and function to misfolded proteins.

Results were published by the Royal Society of Chemistry and featured in Nature Chemistry in June.

Rotello and De exposed three different proteins to heat, causing them to clump together and deactivate. After placing the proteins in a solution containing engineered gold nanoparticles, testing showed that they had regained 93 to 97 percent of their lost function, and refolded to a shape that was close to their original state. The proteins were then released from the nanoparticles by adding salt to the solution, which reduced the attraction between the nanaoparticles and the proteins.

While other methods of rescuing misfolded proteins have been developed, this approach using gold nanoparticles is unique in that it works with the exposed, electrically-charged areas of the denatured protein instead of interacting with the core of the molecule, an area known for its ability to repel water.

Accoding to Rotello, repairing misfolded proteins will have numerous applications. “Medical and biotechnology processes often require the rescue of misfolded proteins, and misfolded proteins are responsible for many diseases, including Mad Cow disease and Alzheimer’s disease,” says Rotello. “Finding a practical solution to the issue of misfolding in the laboratory will be of great importance to biotechnology, and could provide leads for the creation of therapeutics that could be used in human patients.”

July 28, 2008.

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