Tyrosine Phosphatase Inhibitors As New Immunomodulators

The goal of the research is to develop a potent pharmacologically useful inhibitor of the CD45 protein tyrosine phosphatase. CD45 is a transmembrane protein having a highly glycosylated extracellular region and a cytosolic domain which possesses tyrosine phosphatase activity. CD45 plays a critical role in the activation of both T- and B-lymphocytes, thus, inhibitors of CD45 may represent new immunomodulators or anti-inflammatory drugs. We will l) design and synthesize novel inhibitors of the CD45 protein tyrosine phosphatase based on a nonhydrolyzable pseudosubstrate approach, 2) evaluate the new compounds as inhibitors in an in vitro assay. The compounds developed in these studies will greatly increase our knowledge of the structure-activity relationships for protein tyrosine phosphatase inhibitors and may lead to the development of new research tools and therapeutics.