期刊
CURRENT OPINION IN STRUCTURAL BIOLOGY
卷 20, 期 1, 页码 54-62出版社
CURRENT BIOLOGY LTD
DOI: 10.1016/j.sbi.2009.12.009
关键词
-
资金
- NIH [DK46335, A142266]
- Skaggs Institute for Chemical Biology
- Lita Annenberg Hazen Foundation
Small molecules that bind to normally unoccupied thyroxine (T(4)) binding sites within transthyretin (TTR) in the blood stabilize the tetrameric ground state of TTR relative to the dissociative transition state and dramatically slow tetramer dissociation, the rate-limiting step for the process of amyloid fibril formation linked to neurodegeneration and cell death. These so-called TTR kinetic stabilizers have been designed using structure-based principles and one of these has recently been shown to halt the progression of a human TTR amyloid disease in a clinical trial, providing the first pharmacologic evidence that the process of amyloid fibril formation is causative. Structure-based design has now progressed to the point where highly selective, high affinity TTR kinetic stabilizers that lack undesirable off-target activities can be produced with high frequency.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据