Identification of new classes of ricin toxin inhibitors by virtual screening.

ABSTRACT: We used two virtual screening programs, ICM and GOLD, to dock nearly 50,000 compounds into each of two conformations of the target protein ricin A chain (RTA). A limited control set suggests that candidates scored highly by two programs may have a higher probability of being ligands than those in a list from a single program. Based on the virtual screens, we purchased 306 compounds that were subjected to a kinetic assay. Six compounds were found to give modest, but significant, inhibition of RTA. They also tended to inhibit Shiga toxin A chain, with roughly the same IC(50). The compounds generally represent novel chemical platforms that do not resemble RTA substrates, as currently known inhibitors do. These six were also tested in a cell-based assay for their ability to protect cells from

SUBMITTER: Bai Y 

PROVIDER: S-EPMC2929769 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature