Enzyme Inhibitors,
or,
How We Have Been Trying To Find A Cure For The Common Cold
In collaboration with Professor Robert Hanzlik of this department, we have been increasingly interested in designing inhibitors for various peptidase enzymes of biological importance. Peptidases are enzymes that cleave peptide bonds and are essential in processing proteins essential for viral growth as well as in many mammalian processes as well. We have been interested specifically in finding inhibitors of rhinovirus C protease, an essential proteinase in the virus responsible for the common cold. Future efforts will center on calpain, a cysteine protease that has been shown to play important roles in the hypoxic/ischemic cell injury of infarction and stroke and a number of other medically relevant processes.
Some of the structural types of inhibitors that we have explored are shown below.
Lead References
1. Syntheses and Evaluation of Peptidyl Michael Acceptors That Inactivate Human Rhinovirus 3C Protease and Inhibit Virus Replication. Kong, J.-s.; Venkatraman, S.; Furness, K.; Nimkar, S.; Shepard, T. A.; Wang, Q. M.; Aubé, J.; Hanzlik, R. P. J. Med. Chem. 1998, 41, 2579-2587.
2. Design, Synthesis and Evaluation of Azapeptides as Substrates and Inhibitors for Human Rhinovirus 3C Protease. Venkatraman, S.; Kong, J.-s.; Nimkar, S.; Wang, Q. M.; Aubé, J.; Hanzlik, R. P. Bioorg. Med. Chem. Lett. 1999, 9, 577-580.
For More Information Contact:
Department of Medicinal Chemistry
4070 Malott Hall
Tel: 785-864-4495
FAX: 785-864-5326
Internet: jaube@ku.edu
