Development of Novel Protease Inhibitors

Proteases are enzymes that catalyze the hydrolysis of peptide bonds in proteins, a process called proteolysis. Uncontrolled, excessive proteolysis can lead to a large variety of disease states including cancer, cardiovascular, inflammatory, neurodegenerative (Alzheimer’s and Parkinson’s diseases), bacterial, viral (HIV), and parasitic diseases. Excessive proteolysis can be stopped by inhibiting the appropriate proteases.

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 design of inhibitor, where the electrophilic warhead is reactive enough to result in inhibition while staying unreactive toward other off-target proteases or other classes of enzymes.

Dr. 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 certain cancers and neurodegenerative diseases. Novel inhibitors are being designed with the guidance of computer modeling, synthesized utilizing organic chemistry techniques, and evaluated kinetically in vitro.

ImageSource=RCSB PDB; StructureID=2c1e; DOI=;

Caspase-3 in Complex with Aza-peptide Michael Acceptor Inhibitor
PDB Code: 2C1E