ABSTRACT
Transthyretin (TTR) is a human plasma protein associated with different forms of hereditary amyloidosis. In these diseases TTR variants precipitate as amyloid fibrils, extracellularly. Studies indicate that the TTR potency for amyloid formation is related to stability of the tetrameric form of the protein. Iododiflunisal (IDIF), Bromodiflunisal (BrDIF) and Iodoflufenamic acid were produced by chemical modification of the parent compounds. In order to investigate selectivity of TTR stabilizers we started by determining their capacity to compete with T4 for protein binding in plasma. The stabilization effect of IDIF was also evident when tested in the other plasma samples referred to previously. A similar effect was observed in plasma from TTR knockout mice carrying the TTR V30M human gene. The inhibitory effect of IDIF on TTR aggregation was tested using TTR Y78F and compared with the effect with diflunisal. IDIF inhibited TTR aggregation contrary to what was found for the protein incubated with diflunisal.
