Glutathione-S-transferase isoenzymes are involved in the process of multidrug resistance. To evaluate the role of GST in this process, in vivo active, isoenzyme selective inhibitors are of pivotal importance. Glutathione-conjugates are often good GST inhibitors but lack in vivo metabolic stability. In this study, peptidomimetic changes have been made to the glutathione backbone. These compounds are more resistant to peptidase-mediated breakdown. The influence of these structural changes on enzyme-substrate interactions was determined by molecular modelling studies and by in vitro GST inhibition studies. Also a series of (hetero) cyclic compounds was coupled to a GSH-mimic to investigate hydrophobic-binding site interactions.
|Publication status||Published - 2001|