Alzheimer's disease (AD), the most common form of dementia in elderly humans, can be characterized by the presence of amyloid-� (A�) plaques within the brain. Metal ions such as Cu(II) and Zn(II) can be observed co-localized with these misfolded protein aggregates and are suggested to bind to the A� peptide (metal-A� species). Metal-A� species are proposed to contribute to AD onset and progression but a clear relationship remains elusive mainly due to the lack of chemical tools to specifically target them. To advance this understanding, two families of bifunctional compounds have been developed by our laboratory via a rational structure-based design strategy. These compounds are capable of modulating various modes of metal-A� reactivity and show promise for the continued development of new chemical reagents for investigating metal-A� chemistry and biology in AD. Here, the design, synthesis, characterization, and reactivity of the newly prepared bifunctional molecules will be presented.

Development of two families of bifunctional small molecules that target and modulate the reactivity of metal-A<i>β</i> species

243rd National Meeting (2012)

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Development of two families of bifunctional small molecules that target and modulate the reactivity of metal-Aβ species