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Covalent modification of enzymes can be effected by ADP-ribosylation reactions. Examples in this regard are represented, in prokaryotes, by elongation factor 2 (EF-2) of protein synthesis, a peptidyl transferase that is inhibited when acted upon in the presence of NAD+ by diphteria toxin, which is endowed with pApase activity (Honjo et al. 1971); as a result, protein synthesis is blocked. A similar mechanism operates in the infection by Pseudomonas aeruginosa, the toxin of which also promotes ADP-ribosylation of EF-2 (Iglewski and Kabat 1975). Also T4 phage-infected E. coli RNA-polymerase is modified, and thereby inhibited, by ADP-ribosylation at arginine residues of the α subunits (Goff 1974). A modification of the adenylate cyclase system has been recently found in a number of instances; it would appear that ADP-ribosylation of the GTP-binding protein component of that system leads to reduction of GTP hydrolysis, and thereby to enhanced adenylate cyclase activity (Gill et al. 1979). In eukaryotes, a Ca++, Mg++-dependent endonuclease of rat liver nuclei has been reported by Yoshihara et al. (1975) to be ADP-ribosylated by an enzyme preparation from the same tissue.

Many experimental data have been obtained regarding the physiological functions of poly(ADP-ribosyl)ation reactions. DNA replication, cell differentiation, transformation of cells, and DNA repair are among the processes in which poly(ADP-ribosyl)-ation is thought to be involved [1–3]. Inhibitors of ADP-ribosyltransferase (ADPRT) have been very useful in the attempt to ascribe a physiological role to these reactions in various cellular functions. 3-Aminobenzamide and 3-methoxybenzamide have been shown to be powerful competitive inhibitors of ADPRT [4]. Some experimental data obtained with the use of these inhibitors clearly indicate that poly(ADP-ribosyl)ation reactions are indeed crucial for cell differentiation [3] and the DNA strand break rejoining process [5]. On the other hand, the use of inhibitors often meets inconveniences in that their effects are not always limited to the desired metabolic pathway [6]. Tanaka et al. [7] have recently reported that diadenosine tetraphosphate, a ligand of a subunit of DNA polymerase α, could act as a very efficient inhibitor of ADPRT, but further data concerning its involvement in ADP-ribosylation reactions have not been reported so far. Poly amines, such as spermine and spermidine, are also known to have inhibitory effects on ADP-ribosylation of histone H1 [8], although their usefulness as a specific inhibitor of ADPRT remains doubtful. In the light of this circumstance, we have tried to examine the effect of various 2′,5′-oligoadenylates (2′,5′A) on the activity of ADPRT.