DOHH (deoxyhypusine hydroxylase) Inhibitors

Deoxyhypusine hydroxylase (DOHH) is an enzyme that plays a critical role in the post-translational modification of eukaryotic initiation factor 5A (eIF5A) through the hypusination process. Hypusination, unique to eIF5A, involves the initial addition of a spermidine-derived aminobutyl group to a specific lysine residue by deoxyhypusine synthase (DHS), followed by the hydroxylation of this adduct by DOHH. This modification of eIF5A is essential for its role in protein synthesis, particularly in the elongation step of mRNA translation. DOHH's activity is iron-dependent and sensitive to oxygen levels, indicating its potential involvement in cellular responses to oxidative stress. Furthermore, the hypusination of eIF5A by DOHH has been linked to cell proliferation, differentiation, and apoptosis, highlighting its significance in various cellular processes and disease states, including cancer and viral infections.

Targeting DOHH for disruption or inhibition with small molecules allows for a detailed examination of the hypusination process and its role in cellular functions. By inhibiting DOHH, researchers can specifically disrupt eIF5A hypusination, providing insights into the importance of this modification in protein synthesis and cell growth. Such studies can reveal the consequences of impaired eIF5A function, deepening our understanding of its role in cellular physiology and pathology. Additionally, exploring the inhibition of DOHH offers potential avenues, particularly in conditions where altered protein synthesis is a factor, such as in cancer or viral replication.