Pateamine

Pateamine refers to a family of marine natural products that includes pateamine A and pateamine B. These compounds are isolated from marine sponges and are characterized by a macrocyclic lactone framework. They exhibit potent bioactivity in vitro, notably cytotoxic effects against cancer cell lines, and have been used as chemical probes to study translation initiation.

Mechanism of action: Pateamine A and related members act by binding to the eukaryotic initiation factor 4A (eIF4A), a DEAD-box RNA helicase required for cap-dependent translation. Binding promotes a stable eIF4A–RNA complex and inhibits helicase activity, leading to suppression of cap-dependent translation and reduced protein synthesis. This translational stress can trigger apoptosis in susceptible cells.

Biological activity and research: In cell culture, pateamines show potent cytotoxicity across diverse cancer cell types, and exhibit antiviral activity in some systems by blocking viral protein synthesis. However, due to broad effects on host translation, toxicity limits their therapeutic use; research focuses on understanding the mechanism and developing derivatives with improved selectivity or use as research tools.

Chemistry and synthesis: Pateamines are subjects of total synthesis and structure-activity relationship (SAR) studies. Synthetic analogs and affinity probes have been developed to elucidate interaction with eIF4A and to explore SAR, aiding mechanistic understanding and the search for more selective tools.

Potential and limitations: While informative for studying translation initiation and as a basis for therapeutic exploration, clinical development of pateamines has been constrained by toxicity and the challenge of achieving selective modulation of translation.