Interaction of the human leukocyte proteinases elastase and cathepsin G with gold, silver and copper compounds.
Gold thiomalate and the corresponding silver and copper derivatives were investigated as inhibitors of the human leukocyte proteinases elastase and cathepsin G. The kinetic inhibition mechanism for gold- and silver thiomalate is of the hyperbolic non-competitive type with both enzymes and the inhibitory efficiency of the metals increases in the order Cu less than Ag less than Au. On the contrary, D-penicillamine derivatives of the three metals do not influence at all the activity of the two proteinases. Although gold thiomalate is the most efficient of the investigated metal compounds (Ki = 33 microM and 25 microM for elastase and cathepsin G, respectively), the hyperbolic nature of the inhibition imposes a serious limit to its practical usefulness since the maximum inhibitory action on both enzymes is about 40%. We suggest that, in order to act as inhibitor, a copper, silver or gold compound must be able to easily transfer the metal to the enzyme.
D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003300:Copper / Q000494:pharmacology*; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010396:Penicillamine / Q000494:pharmacology; D012697:Serine Endopeptidases; D012834:Silver / Q000494:pharmacology*
D006052:Gold Sodium Thiomalate; D012834:Silver; D003300:Copper; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D010396:Penicillamine