LSA Biophysics pres.
Biophysics Seminar Series
Dr. Michele Vendruscolo (University of Cambridge)
Dr. Michele Vendruscolo - Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge
“Activity Relationship by Kinetics for Drug Discovery in Protein Misfolding Diseases”
ABSTRACT: Protein oligomers are increasingly recognized as the most cytotoxic forms of protein aggregates. It has been very challenging, however, to target these oligomers with therapeutic compounds, because of their dynamic and transient nature. To overcome this problem, I will describe a 'structure kinetic-activity relationship' (SKAR) approach, which enables the discovery and systematic optimization of compounds that reduce the number of oligomers produced during an aggregation reaction. I will illustrate this strategy for the amyloid beta peptide, which is closely associated with Alzheimer's disease, by developing a rhodanine compound capable of dramatically reducing the production of amyloid beta oligomers. As this strategy is general, it can be applied to oligomers of any protein.
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