NOVEL INHIBITORS OF POLY(ADP-RIBOSE) GLYCOHYDROLASE

The inhibitory effects on poly(ADP-ribose) glycohydrolase purified fro m human placenta of three classes of chemically defined tannins; gallo tannins, ellagitannins and condensed tannins, were examined in vitro. Oligomeric ellagitannins were found to be most potent inhibitors of po ly(ADP-ribose) glycohydrolase, their potencies increasing with increas ing number of monomeric residues (dimer < trimer < tetramer). Monomeri c ellagitannins and gallotannins were less inhibitory. Condensed tanni ns, which consist of an epicatechin gallate oligomer without a glucose core, were not appreciably inhibitory. A structure-activity study sho wed that higher-order conformations of the conjugates with glucose of hexahydroxydiphenoyl and varoneoyl groups, which are unique components of ellagitannins, cooperatively potentiated the inhibitory activity.