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Studies on the inhibition of ellagic acid-activated Hageman factor (factor XII) and Hageman factor fragments
Authors:Ratnoff   OD
Abstract:Hageman factor (HF, factor XII) that has been exposed to Sephadex- ellagic acid gels is a single-chain species (HFea) with amidolytic properties for the synthetic substrate H-D-phenylalanyl-L-pipecolyl-L- arginine p-nitroanilide. Earlier we reported that amidolysis was suppressed by incubation of HFea with specific antiserum. The present study provides additional evidence that the amidolytic properties of preparations of HFea are ascribable to this substance through an examination of a number of protease inhibitors. HFea's amidolytic properties were inhibited by alpha 2-plasmin inhibitor, antithrombin III in the presence of heparin, and Cl esterase inhibitor (Cl-INH). Additionally, it was inhibited by popcorn inhibitor, leupeptin, hexadimethrine bromide, protamine sulfate, dansyl-arginine N-(3-ethyl- 1,5-pentanediyl) amide (DAPA), diisopropylphosphofluoridate (DFP), aprotinin, and at excessively high concentrations, soybean and lima bean trypsin inhibitors. The spectrum of action of agents that did or did not inhibit HFea supports the view that amidolysis by preparations of HFea is attributable to this enzyme. In general, the enzymatically active carboxy-terminal fragment of HF (HFf) was inhibited by the same agents that inhibited HFea, but aprotinin, protamine sulfate and hexadimethrine bromide were more effective against HFf than HFea, while the reverse was true of lima bean trypsin inhibitor.
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