Amyloid-beta (Aβ) plays an important role in the pathogenesis of Alzheimer’s disease. As Aβ accumulates, misfolded monomers arise promoting the recruitment of additional peptides to this unique, misfolded conformation. These misfolded monomers are far more prone to aggregation than the native Aβ species, inducing the formation of oligomers, and eventually larger species of Aβ called fibrils and plaques. The intermediates of this process are thought to be more deleterious than their larger plaque counterparts, due to their solubility and potential to block neuronal synapses and disrupt cellular signaling. Ample research has been conducted to examine the deleterious properties of Aβ; however, too little is known concerning the transition of Aβ to its misfolded conformer. As an intrinsically unstructured protein, Aβ(42) does not have a specific tertiary form. Rather, the peptide sequence adapts a series of conformations depending on what is thermodynamically favorable. There is evidence to suggest that the misfolded conformation of Aβ(42) has a far more defined structure than native Aβ(42). The problem arises in the misfolded form’s ability to aggregate quickly, before the structure of the misfolded monomer can be studied in detail. This renders quantitative characterization techniques such as X-ray crystallography somewhat useless unless a procedure is developed to strategically immobilize the Aβ for analysis. We propose the use of metal-organic frameworks (MOFs) as mechanisms to adsorb and sequester Aβ(42). As a class of highly porous materials comprised of metal clusters and organic ligands, MOFs have numerous characteristics that make them suitable for peptide adsorption. The propensity of MOFs to adsorb a diverse array of small organic molecules by means of tailoring them to possess the desired structural characteristics and functionality affirms their viability.

Synthesis of metal-organic frameworks for adsorption of disease-relevant peptides

249th National Meeting (2015)

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