Chemistry Weekly Seminar-Ed S. Krol, Pharmaceutical and Nutrition Sciences Research Group, College of Pharmacy & Nutrition

Title

Investigating a-synuclein misfolding with chemical probes.

Abstract

a-Synuclein is a 140 amino acid containing protein which is believed to play a role in synaptic vesicle trafficking in the brain however, aggregates of a-synuclein are present in Lewy Bodies found in the brains of Parkinson’s Disease patients. It is believed that aggregation of a-synuclein monomers is a contributing factor to Parkinson’s Disease. One strategy that has been pursued for a number of years has been to identify compounds that inhibit a-synuclein aggregation as possible therapeutic agents to halt the progression of Parkinson’s Disease. My group has been involved in the synthesis and assessment of compounds that have demonstrated the ability to bind to a-synuclein monomers in vitro. a-Synuclein is considered disordered and because of this, identification of binding interactions are difficult to assess. In an effort to address this we are designing probes to gain an understanding of where on the protein our compounds interact. In addition to preventing a-synuclein aggregation, a second area of interest is identifying compounds that can selectively bind to the aggregates of a-synuclein and can be used as diagnostics for Parkinson’s Disease. We have used pharmacophore modelling to guide design of compounds that are amenable to labelling with 18F in order to explore the use of Positron Emission Tomography for diagnostic imaging.