title: Interaction of the human leukocyte proteinases elastase and cathepsin G with gold, silver and copper compounds.
abstract: 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.
mesh_terms: 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*
chemical_list: 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