Structure-Based Design of Inhibitors to the Cytotoxin RICIN. Addendum
Final rept. 15 Jun 2003-14 Nov 2007
TEXAS UNIV AT AUSTIN
Pagination or Media Count:
Ricin is a cytotoxin and a known bioterrorist weapon. The Army is pursuing anti-ricin vaccines, but plans to develop an efficacious antidote to the toxin for cases where vaccination is not appropriate. The goal of this project was to use the X-ray structure of ricin. A chain RTA as a template for inhibitor design. Computer modeling and X-ray screening aid in the design process. inhibitors which bind to the RTA substrate specificity site have been identified. Several chemical platforms including 9-oxo-guanine and 9-deazaguanine have been shown to bind in the RTA active site and act as a weak inhibitors. However efforts to derivatize and diversify the platforms via several straties including triazole click chemistry have met with unanticipated difficulties. None of the new compounds exhibits greatly improved inhibitory properties. A virtual screen of available compounds suggests pyrimidines may provide a useful platform for future work.
- Anatomy and Physiology
- Medicine and Medical Research