title: Novel inhibitors of poly(ADP-ribose) glycohydrolase.
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.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Aoki
authors.forename: K
authors.initials: K
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Maruta
authors.forename: H
authors.initials: H
authors.lastname: Sakagami
authors.forename: T
authors.initials: T
authors.lastname: Hatano
authors.forename: T
authors.initials: T
authors.lastname: Okuda
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: Y J
authors.initials: YJ
authors.lastname: Tsai
authors.forename: F
authors.initials: F
authors.lastname: Uchiumi
mesh_terms: D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D047348:Hydrolyzable Tannins; D010920:Placenta / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013634:Tannins / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D013634:Tannins; C013515:ellagitannin; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase