Novel inhibitors of poly(ADP-ribose) glycohydrolase

Biochim Biophys Acta. 1993 Nov 28;1158(3):251-6. doi: 10.1016/0304-4165(93)90022-z.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / pharmacology*
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Humans
  • Hydrolyzable Tannins*
  • Placenta / enzymology*
  • Structure-Activity Relationship
  • Tannins / pharmacology*

Substances

  • Enzyme Inhibitors
  • Hydrolyzable Tannins
  • Tannins
  • ellagitannin
  • Glycoside Hydrolases
  • poly ADP-ribose glycohydrolase