Development of Novel Protease Inhibitors
Proteases are enzymes that catalyze the hydrolysis of peptide bonds in proteins, a process called proteolysis. Manipulating proteolysis via inhibiting the appropriate proteases offers therapeutic solutions to a large variety of disease states including cancer, cardiovascular, inflammatory, neurodegenerative (Alzheimer’s and Parkinson’s diseases), bacterial, viral (COVID-19, HIV), and parasitic diseases.
Despite the large number of inhibitors that have been designed for proteases, currently only a few classes of inhibitors are specific for their target protease. The challenge is to develop a unique drug-like inhibitor, where it is reactive enough to result in inhibition while staying unreactive toward other off-target proteases or other classes of enzymes.
Dr. Dogan Ekici is interested in developing synthetic inhibitors for proteases utilizing rational drug design. Currently, she is focusing on cysteine and threonine proteases that are validated as therapeutic targets for the treatment of COVID-19, certain cancers and neurodegenerative diseases. Dr. Dogan Ekici’s research is highly collaborative. Novel inhibitors are being designed with the guidance of computer modeling, synthesized utilizing organic chemistry techniques, and evaluated kinetically in vitro and ex vivo.
Caspase-3 in Complex with Aza-peptide Ketone Inhibitor
(Corrigan T. et. al., J Enz. Inh. & Med Chem., 2020, 35 (1), 1387-1402)