Synthesis of Pateamine A Derivatives for Putative Cellular Receptor Isolation and Structure Activity Studies

Molecules that inhibit the immune responses by blocking a specific signaling pathway involved in T-cell activation have proven to be useful biochemical tools. In this regard, molecules such as FK-506, cyclosporin A and rapamycin have aided in the elucidation of pathways which trigger the immune response as well as molecules involved along the signaling pathway .으 Pateamine A, a potent immunosuppressant isolated from the M ycale species sponge, was found to inhibit an intracellular step of the T-cell receptor signal transduction pathway leading to EL-2 production. Although the detailed signaling pathway affected by pateamine A has not been determined, pateamine A is an attractive candidate for use as a biological probe in the study of T-cell signaling pathways, and thus the isolation of its putative cellular receptor may provide a novel therapeutic target for intervention in autoimmnue diseases.