Photoactive Metal Complexes for Sensing, Study and Inhibition of Amyloid-β Aggregation

Friday, September 6, 2019 - 1:10pm
Event Type: 

Angel Martí

Department of Chemistry, Rice University



Protein misfolding and aggregation mark the onset of a variety of neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD). For AD in particular, different stages in the misfolding and aggregation of amyloid-b (Ab) has been related to the development of this disease. Ab is a relatively unstructured peptide of 39 to 42 amino acids in length, which can form soluble (oligomers) and insoluble (fibrils) aggregates. Amyloid-b fibrils possess a cross-b spine with a regular structure surrounded by large random coil regions. The intrinsic degree of disorder in these Ab structures makes the study of its structure and interactions with small molecules using traditional laboratory techniques such as X-ray diffraction and nuclear magnetic resonance (NMR) challenging. Nonetheless, structural information on the binding of small molecules to Ab is necessary for developing better diagnostics and drugs targeting to diminish the deleterious effect of Ab fibrils on neurons. Here we will present our studies on the structure and binding sites of Ab using Re(I) carbonyl dipyridophenazine complexes. These complexes present unprecedented properties for labeling amyloid aggregates, which involve increase in photoluminescence and selective chemical labeling. We have found that amyloid fibrils get photooxidased by the metal complexes nearby the place of binding. In addition, we discovered that rhenium complexes can photooxidize soluble Ab monomers on amino acids that are distinct from those in the fibrils, suggesting a different binding place than for the fibrils. We will discuss how finding these photooxidation can help in elucidating molecular binding sites in soluble and insoluble Ab structures. These photochemical modifications have a profound effect on the folding landscape, as well as the self-assembly and stability of amyloid aggregates