Quantitative studies of inhibitors of ADP-ribosylation in vitro and in vivo.

摘要: The ADP-ribosyl moiety of NAD+ is consumed in reactions catalyzed by three classes enzymes: poly(ADP-ribose) polymerase, protein mono(ADP-ribosyl)transferases, and glycohydrolases. In this study, we have evaluated the selectivity compounds originally identified as inhibitors polymerase on members enzymes. 50% inhibitory concentration (IC50) more than 20 was determined vitro for both mono(ADP-ribosyl)transferase A an assay containing 300 microM NAD+. Of tested, benzamide most potent inhibitor with IC50 3.3 microM. 4.1 mM, similar values were observed four additional cellular mono(ADP-ribosyl)transferases. glycohydrolase approximately 40 mM. For seven best inhibitors, inhibition intact C3H1OT1/2 cells studied a function culture medium, (culture medium IC50) determined. Culture its derivatives very to values. other such nicotinamide, 5-methyl-nicotinamide, 5-bromodeoxyuridine, 3-5-fold higher These results suggest that micromolar levels benzamides should allow selective metabolism cells. Furthermore, comparative quantitative studies prove useful assigning biological effects these effect either or mono(ADP-ribose) metabolism.