Inhibitors and activators of ADP-ribosylation reactions.

ADP-ribosylation reaction, that is the transfer of the ADP-ribose moiety of NAD+ to acceptor protein, is catalyzed by two classes of ADP-ribosyltransferases, i.e., poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferases. These two types differ not only in the number of transferring ADP-ribose units but also in the acceptor amino acid(s) and protein. Their inhibitors, particularly those of poly(ADP-ribose) synthetase, have been successfully employed in studies on biological functions of the enzymes and other related fields of research. Recently, we found many potent and specific inhibitors of poly(ADP-ribose) synthetase, and broadened their chemical as well as biochemical variety. More recently, we found several potent inhibitors of arginine-specific mono(ADP-ribosyl)transferases and activators of poly(ADP-ribose) synthetase.