The hypusine modification that occurs post-translationally in eIF-5A is essential for growth of eukaryotic cells. Knowledge of the enzymological features of hypusine biosynthesis accumulated in this laboratory over the past several years has enabled us to design some effective and specific inhibitors for the enzymes that catalyze hypusine formation. Preliminary successes in controlling cell proliferation were obtained with certain of these inhibitors with little accompanying generalized toxic effects. This encouraged us to attempt to develop even more effective agents to use as drugs and to extend our in vivo studies. In addition, these agents are being applied to further our understanding of the specific cellular functions of hypusine and eIF-5A and to derive fundamental knowledge of the mechanisms of action of the very unusual enzymes involved in hypusine biosynthesis.
