Structure-Based Design of Ricin Inhibitors

摘要: Ricin is a potent cytotoxin easily purified in large quantities. It presents significant public health concern due to its potential use as bioterrorism agent. For this reason, extensive efforts have been underway develop antidotes against deadly poison. The catalytic A subunit of the heterodimeric toxin has biochemically and structurally well characterized, an attractive target for structure-based drug design. Aided by computer docking simulations, several ricin chain (RTA) inhibitors identified; most promising leads belonging pterin family. Development these lead compounds into candidates challenging prospect numerous reasons, including poor solubility pterins, highly polar secondary binding pocket RTA, enzyme’s near perfect efficiency tight affinity natural substrate, eukaryotic ribosome. To date, RTA developed using approach are only modest with apparent IC50 values 10−4 M range, leaving room improvement. This review highlights variety techniques routinely employed design projects, challenges faced inhibitors.