Structure-Based Design of Inhibitors to the Cytotoxin Ricin
Abstract
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 is 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. A platfdrm 9-deazaguanine has been shown to bind in the RTA active site and act as a weak inhibitor. However efforts to derivatize and diversify the platform via 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 catechols may provide a novel platform for future work.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA469261
Entities
People
- Jon Robertus
Organizations
- University of Texas at Austin