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Scientists find new drug candidates for set of protein-folding diseases
Date:8/29/2011

LA JOLLA, CA August 29, 2011 Collaborating researchers at Stanford University and The Scripps Research Institute have identified chemical compounds that show promise as potential therapeutics for a set of medical conditions caused by the abnormal clumping together of a protein known as transthyretin (TTR).

The compounds, which prevent the abnormal aggregation of the TTR protein, work by holding the protein together in its functional form. These compounds have the potential one day to help the hundreds of thousands of people who have TTR-related amyloid diseases or are at risk for them, and may have advantages over other TTR-stabilizing drugs, which are currently in clinical trials.

"These new compounds have structures that make them very effective at stabilizing TTR in its stable native tetrameric form in laboratory tests, and they also seem nontoxic in cell culture," said Stephen Connelly, a senior research associate in the Scripps Research laboratory of Professor Ian Wilson.

Connelly, who determined the molecular structures of these TTR-stabilizing compounds, is a co-lead-author of the report, which appears in the current issue of Science Translational Medicine. The other lead author is Mamoun M. Alhamadsheh, who at the time of the study was a postdoctoral researcher in the laboratory of Isabella Graef, an assistant professor of pathology at Stanford University.

Defenses against Abnormal Forms

TTR proteins normally don't work alone. Single "monomeric" copies come together in pairs, and then in pairs of these pairs, to form four-protein structures known as "tetramers." Secreted by the liver into the bloodstream, TTR tetramers work as transporters of the hormone thyroxine and also bind the holo retinal binding protein. In the hustle and bustle of the bloodstream, however, TTR tetramers often come apart, and when that happens, the naturally sticky individual TTR proteins may start to re-form abnormal
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

Page: 1 2 3

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