Insights On The Interaction Between Transthyretin And A Beta In Solution. A Saturation Transfer Difference (Std) Nmr Analysis Of The Role Of Lododiflunisal

Several strategies against Alzheimer disease (AD) are directed to target A beta-peptides. The ability of transthyretin (TTR) to bind A beta-peptides and the positive effect exerted by some TTR stabilizers for modulating the TTRA beta interaction have been previously studied. Herein, key structural features of the interaction between TTR and the A beta(1228) peptide (3), the essential recognition element of A beta, have been unravelled by STD-NMR spectroscopy methods in solution. Molecular aspects related to the role of the TTR stabilizer iododiflunisal (IDIF, 5) on the TTRA beta complex have been also examined. The NMR results, assisted by molecular modeling protocols, have provided a structural model for the TTRA beta interaction, as well as for the ternary complex formed in the presence of IDIF. This basic structural information could be relevant for providing light on the mechanisms involved in the ameliorating effects of AD symptoms observed in AD/TTR +/- animal models after IDIF treatment and eventually for designing new molecules toward AD therapeutic drugs.