Some protease inhibitors are also inhibitors of poly(ADP-ribose) polymerase.
The low-molecular-weight peptide protease inhibitors, tosyl-lysine-chloromethyl ketone, antipain and leupeptin, inhibited poly(ADP-ribose) [poly(ADP-Rib)] polymerase in permeable cells. The concentrations required for 50% inhibition were 3.6, 5 and 29 mM, respectively. Two peptides without protease inhibitor activity, fibrinopeptide A and phenylalanine-leucine-(glutamine)2-leucine, also inhibited poly (ADP-Rib) synthesis; doses required for 50% inhibition were 0.37 and 11.2 mM, respectively. These concentrations lie within a range bracketed by the 50% inhibition concentrations of the strong and weak poly(ADP-Rib) synthesis inhibitors, 3-amino-benzamide (0.15 mM) and caffeine (greater than 100 mM), respectively. N-Ethylmaleimide also inhibited poly(ADP-Rib) synthesis, at a 50% inhibitory dose of 0.3 mM, in the absence of exogenous thiol reagents. High-molecular-weight protease inhibitors, such as soybean (including Bowman-Birk reagent) and lima bean trypsin inhibitors and human alpha 1-protease inhibitor, had no effect on poly(ADP-Rib) synthesis up to 2 mg/ml. Interference with transformation and other cellular effects that have been reported in carcinogen-damaged cells treated with low-molecular-weight peptide protease inhibitors may therefore involve common mechanisms with poly(ADP-Rib) inhibitors. Similar effects of high-molecular-weight protease inhibitors presumably involve different mechanisms.
Cleaver
J E
JE
Banda
M J
MJ
Troll
W
W
Borek
C
C
D000976:Antipain / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology*
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011480:Protease Inhibitors; D000976:Antipain; D002110:Caffeine; C025160:3-aminobenzamide; D008741:Methyl Methanesulfonate