An improved nonisotopic test to screen a large series of new inhibitor molecules of poly(ADP-ribose) polymerase activity for therapeutic applications

A reliable ELISA for screening large numbers of poly(ADP-ribose) polymerase (PARP) inhibitors is described, The test is based upon the drop in PARP ac tivity estimated by the decrease in poly(ADP-ribose) synthesis in the prese nce of inhibitor. This ELISA is easy to perform, rapid, and specific. It is extremely sensitive because a clear inhibition of the total reaction could be visualized with molecules used in the nanomolar range. The assay uses n o radioactivity, and automation is possible with robots for large-scale inv estigations. This test is of great interest for the screening of chemical l ibraries and the discovery of new inhibitors (and possibly activators) of P ARP, Such molecules have important applications in all abnormal situations involving DNA damage and oxidative stress, such as cancer, autoimmunity, di abetes, myocardial dysfunctions, certain infections, aging, and radiation/c hemical exposure.