NMR Reveals Two-Step Association of Congo Red to Amyloid ? in Low-Molecular-Weight Ag

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NMR Reveals Two-Step Association of Congo Red to Amyloid ? in Low-Molecular-Weight Aggregates.

Related Articles NMR Reveals Two-Step Association of Congo Red to Amyloid ? in Low-Molecular-Weight Aggregates.

J Phys Chem B. 2010 Nov 15;

Authors: Pedersen MO, Mikkelsen K, Behrens MA, Pedersen JS, Enghild JJ, Skrydstrup T, Malmendal A, Nielsen NC

Aggregation of the Amyloid ? peptide into amyloid fibrils is closely related to development of Alzheimer's disease. Many small aromatic compounds have been found to act as inhibitors of fibril formation, and have inspired the search for new drug candidates. However, the detailed mechanisms of inhibition are largely unknown. In this study, we have examined in detail the binding of the fibril-formation inhibitor Congo Red (CR) to monomeric A?(1-40) using a combination of 1D, 2D, saturation transfer difference, and diffusion NMR, as well as dynamic light scattering experiments. Our results show that CR binds to the fibril forming stretches of A?(1-40) monomers, and that complex formation occurs in two steps: An initial 1:1 CR:A?(1-40) complex is formed by a relatively strong interaction (K(d) ? 5 ?M), and a 2:1 complex is formed by binding another CR molecule in a subsequent weaker binding step (K(d) ? 300 ?M). The size of these complexes is comparable to that of A?(1-40) alone. The existence of two different complexes might explain the contradictory reports regarding the inhibitory effects of CR on the fibril-formation process.

PMID: 21077638 [PubMed - as supplied by publisher]



Source: PubMed