Iodine atoms: a new molecular feature for the design of potent transthyretin fibrillogenesis inhibitors.

ABSTRACT: The thyroid hormone and retinol transporter protein known as transthyretin (TTR) is in the origin of one of the 20 or so known amyloid diseases. TTR self assembles as a homotetramer leaving a central hydrophobic channel with two symmetrical binding sites. The aggregation pathway of TTR into amiloid fibrils is not yet well characterized but in vitro binding of thyroid hormones and other small organic molecules to TTR binding channel results in tetramer stabilization which prevents amyloid formation in an extent which is proportional to the binding constant. Up to now, TTR aggregation inhibitors have been designed looking at various structural features of this binding channel others than its ability to host iodine atoms. In the present work, greatly improved inhibitors have been designed and

SUBMITTER: Mairal T 

PROVIDER: S-EPMC2607018 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature