Insights on the Interaction between Transthyretin and A? in Solution. A Saturation Transfer Difference (STD) NMR Analysis of the Role of Iododiflunisal.
 

Insights on the Interaction between Transthyretin and A? in Solution. A Saturation Transfer Difference (STD) NMR Analysis of the Role of Iododiflunisal.

http://www.bionmr.com//www.ncbi.nlm....ed-acspubs.jpg Related Articles Insights on the Interaction between Transthyretin and A? in Solution. A Saturation Transfer Difference (STD) NMR Analysis of the Role of Iododiflunisal.

J Med Chem. 2017 Jul 13;60(13):5749-5758

Authors: Gimeno A, Santos LM, Alemi M, Rivas J, Blasi D, Cotrina EY, Llop J, Valencia G, Cardoso I, Quintana J, Arsequell G, Jiménez-Barbero J

Abstract
Several strategies against Alzheimer disease (AD) are directed to target A?-peptides. The ability of transthyretin (TTR) to bind A?-peptides and the positive effect exerted by some TTR stabilizers for modulating the TTR-A? interaction have been previously studied. Herein, key structural features of the interaction between TTR and the A?(12-28) peptide (3), the essential recognition element of A?, 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 TTR-A? complex have been also examined. The NMR results, assisted by molecular modeling protocols, have provided a structural model for the TTR-A? 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.


PMID: 28587455 [PubMed - indexed for MEDLINE]



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