Inhibition of nuclear protein kinases by adenosine analogues

Two cyclic AMP-independent protein kinases from rat liver nuclei were inhibited competitively by adenosine and a variety of its analogues: cardycepin, tubercidin, 6-mercaptopurine riboside, 6-methylaminopurine riboside, 6-dimethylaminopurine riboside, and 2'-deoxyadenosine. Neither enzyme was inhibited by 6-methoxypurine riboside. Kinase NI was more sensitive to cordycepin, tubercidin, 6-methylaminopurine riboside,, 2'-deoxyadenosine, and adenosine than was kinase NII. Although the effects of all analogues tested were reversed by increasing the concentration of ATP, kinases NII and NI exhibited marked differences in their affinities for adenosine. The results presented here suggest that 1) differences in the catalytic properties of nuclear protein kinases can be detected by inhibitor studies and 2) modifications in the purine ring and sugar moiety of an adenosine analogue can alter its ability to inhibit nuclear protein kinases.