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Research offers new way to target shape-shifting proteins
Date:8/28/2011

A molecule which can stop the formation of long protein strands, known as amyloid fibrils, that cause joint pain in kidney dialysis patients has been identified by researchers at the University of Leeds.

The discovery could lead to new methods to identify drugs to prevent, treat or halt the progression of other conditions in which amyloid fibrils play a part, including Alzheimer's, Parkinson's and Type II diabetes.

The research, funded by the Biotechnology and Biological Sciences Research Council and the Wellcome Trust, is published today (August 28) in Nature Chemical Biology.

The team from Leeds' Astbury Centre for Structural Molecular Biology and Faculty of Biological Sciences found that an antibiotic known as Rifamycin SV was able to prevent the protein β2microglobulin (β2m) from forming into fibrils. β2m is known to accumulate in renal dialysis patients and forms fibrils within the joints, causing extreme pain and arthritis.

By using a specialised analytical technique called ion mobility spectrometry-mass spectrometry (IMS-MS), the researchers were able to see at what stage of the process Rifamycin SV prevented amyloid fibril formation. They believe the technique could enable potential drugs to be identified for the many other proteins which form amyloid fibrils, linked to a wide range of human disorders.

"Traditional drug design for diseases like Alzheimer's is incredibly difficult because the proteins you're trying to target are changing shape and structure all the time," explains University of Leeds Professor of Structural Molecular Biology, Sheena Radford. "It's like trying to consistently pick out one bead of a particular shape from box of potentially millions of similar beads. This new technique allows us to see the shape of the protein as it changes, so we can more easily identify exactly which part we need to target."

In their normal, folded state, proteins are unable to link together to form long fibrilla
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Contact: Abigail Chard
abigail@campuspr.co.uk
44-079-604-48532
University of Leeds
Source:Eurekalert

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