The goal of the proposed 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. In this proposal 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.
