Novel inhibitors of poly(ADP-ribose) glycohydrolase.
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.
Aoki
K
K
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Nishimura
K
K
Abe
H
H
Maruta
H
H
Sakagami
H
H
Hatano
T
T
Okuda
T
T
Yoshida
T
T
Tsai
Y J
YJ
Uchiumi
F
F
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*
D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D013634:Tannins; C013515:ellagitannin; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase