ABSTRACT
Transthyretin (TTR) is a plasma protein which is known to form fibrillar extracellular deposits in patients suffering from three main types of pathologies, namely Senile Systemic Amyloidosis, Familial Amyloidotic Cardiomyopathy and Familial Amyloidotic Polyneuropathy. Dissociation of the TTR tetramer is probably essential in the mechanism of amyloid formation and since the binding of small molecules to the TTR central channel stabilizes the tetramer, several compounds are being studied as a prospect for a non invasive therapeutic approach. Diethylstilbestrol (DES) is a synthetic estrogen that was shown to be a competitive inhibitor for thyroid hormone binding to TTR and therefore it may have a stabilizing effect over the protein quaternary structure. The chapter describes the three-dimensional structure of the TTR-DES complex by X-ray crystallography with the aim of identifying the key features of DES that are responsible for its ability to bind TTR.
