We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Prevention of transthyretin amyloid disease by changing protein misfolding energetics.
- Authors
Hammarström, Per; Wiseman, R Luke; Powers, Evan T; Kelly, Jeffery W
- Abstract
Genetic evidence suggests that inhibition of amyloid fibril formation by small molecules should be effective against amyloid diseases. Known amyloid inhibitors appear to function by shifting the aggregation equilibrium away from the amyloid state. Here, we describe a series of transthyretin amyloidosis inhibitors that functioned by increasing the kinetic barrier associated with misfolding, preventing amyloidogenesis by stabilizing the native state. The trans-suppressor mutation, threonine 119 --> methionine 119, which is known to ameliorate familial amyloid disease, also functioned through kinetic stabilization, implying that this small-molecule strategy should be effective in treating amyloid diseases.
- Publication
Science (New York, N.Y.), 2003, Vol 299, Issue 5607, p713
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1079589