Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To establish quantitative structure-activity relationships for the inhibition of trypsin, plasmin and thrombin by 4-amidinophenyl compounds with a keto group, attempts have been made to detect correlations between data on inhibition and substituent constants. The inhibitor activity of the derivatives is described by lipophilic or steric substituent constants using linear free energy relationships. To describe the action of beta-ketones, an additional sigma I term is necessary. The lipophilic or steric term stands for binding of the inhibitor side chain to a second hydrophobic binding site of the enzyme. The electronic term describing inductive influences on the keto group suggests the contribution of the beta-keto group to the enzyme inhibitor binding via a tetrahedral conformation of the carbonyl carbon.
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PMID:[Synthetic inhibitors of serine proteinases. 13. Quantitative structure-activity relationship for inhibition of trypsin and thrombin by 4-amidinophenyl compounds with a ketone structure]. 14 58

alpha2-plasmin inhibitor is a proteinase inhibitor in plasma which efficiently inhibits the lysis of fibrin clots induced by plasminogen activator. The nature of the binding of the inhibitor to trypsin or plasmin was studied by the chemical treatment of the enzyme-inhibitor complex with 7.5 M hydrazine at pH 10.0. With the hydrazine treatment, the complexes were degraded to proteins corresponding to the respective enzyme and inhibitor moieties. These results indicate that the covalent bond between the inhibitor and the enzymes is a carboxylic ester. The binding reaction of the inhibitor to active site-modified trypsin was also studied. The inhibitor formed complexes with anhydrotrypsin and carboxyamidomethylated trypsin. The complexes were dissociated in the presence of 1% sodium dodecyl sulfate, to the individual components: the respective enzyme and inhibitor moieties. The inhibitor, however, did not form a complex with diisopropylphosphorylated trypsin regardless of the presence or absence of the denaturing reagent. These results suggest the contribution of non-covalent interactions to the complex formation between the inhibitor and native enzymes.
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PMID:On the interaction of alpha2-plasmin inhibitor and proteases. Evidence for the formation of a covalent crosslinkage and non-covalent weak bondings between the inhibitor and proteases. 14 46

p-Carbethoxyphenyl episol-guanidinocaproate and p-(p'-guanidinobenzoyloxy)-phenyl derivatives were prepared, and their inhibitory effects on trypsin, plasmin, plasma kallikrein, thrombin, C1r- and C1 esterase were examined. Among the various inhibitors tested, p-nitrophenyl p'-guanidinobenzoate, N,N-dimethylamino p-(p'-guanidinobenzoyloxy)-benzoyl glycolate and N,N-dimethylamino p-(p'-guanidinobenzoyloxy)-benzilcarbonyloxy glycolate were the most effective inhibitors of trypsin, plasmin, plasma kallikrien and thrombin, and they strongly inhibited the esterolytic activities of C1r- and C1 esterase.
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PMID:Synthetic inhibitors of trypsin, plasmin, kallikrein, thrombin, C1r-, and C1 esterase. 14 65

The inhibition of plasmin, (EC 3.4.21.7), thrombin (EC 3.4.21.5), trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1) by antiplasmin, the recently described fast-reacting plasmin inhibitor of human plasma, was studied. To determine the quantitative importance of antiplasmin relative to the other plasma protease inhibitors, enzyme inhibition assays were performed on whole plasma and on plasma specifically depleted in antiplasmin, after addition of excess enzyme. Plasmin was the only enzyme for which the inhibitory capacity of antiplasmin-depleted plasma was lower than that of normal plasma. To determine the affinity of the enzymes for antiplasmin, as compared to the other inhibitors, various amounts of enzymes were added to normal plasma and the formation of enzyme-antiplasmin complexes studied by crossed immunoelectrophoresis using specific antisera against antiplasmin. Plasmin and trypsin, but not thrombin or chymotrypsin formed complexes with antiplasmin. It is concluded that antiplasmin is the only fast-reacting plasmin inhibitor of human plasma. It is also a fast-reacting inhibitor of trypsin but only accounts for a very small part of the fast-reacting trypsin-inhibitory activity of plasma. This can be explained by the low concentration of antiplasmin (1 muM) in normal plasma, compared to the other inhibitors (e.g. alpha1-antitrypsin: 40-80 muM).
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PMID:The interaction in human plasma of antiplasmin, the fast-reacting plasmin inhibitor, with plasmin, thrombin, trypsin and chymotrypsin. 14 66

The authors studied the influence of proteolytic enzymes and arachidonic acid on the erythrocyte and platelet aggregation. These substances stimulated the blood formed elements aggregation. At the same time preliminary incubation of fibrinolysin, trypsin and arachidonic acid with the blood formed elements suspension was accompanied by a significant reduction of their aggregation capacity, i.e. by the development of a refractory condition. A possible mechanism of this phenomenon is discussed.
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PMID:[Refractory nature of erythrocytes and thrombocytes]. 14 52

Rates of hydrolysis of the newly developed peptide chromogenic substrates S-2160 (N-Bz-Phe-Val-Arg-pNA, HCl), S-2238 (H-D-Phe-Pip-Arg-pNA, 2HCl), S-2222 (N-Bz-Ile-Glu-Gly-Arg-pNA, HCl), and S-2251 (H-D-Val-Leu-Lys-pNA, 2HCl) from AB Kabi Peptide Research and Chromozym TH (Z-Gly-Pro-Arg-pNA, HCl) from Pentapharm Limited were tested against highly purified preparations of human plasmin, bovine trypsin, human alpha thrombin, and bovine factor Xa. S-2160, S-2238, and Chromozym TH are sensitive to thrombin, Chromozym TH and S-2238 exhibiting a substantially greater sensitivity than S-2160. All 3 substrates are insensitive to factor Xa but hydrolyzed to varying degrees by plasmin and trypsin. In contrast, S-2222 is sensitive to Xa and insensitive to thrombin. S-2251 is relatively plasmin-specific, being resistant to the clotting enzymes thrombin and Xa. S-2251 exhibits even greater sensitivity to the SK-plasmin complex than to plasmin. In addition, the substrate Chromozym PK (N-Bz-Pro-Phe-Arg-pNA, HCl) was evaluated and found to be relatively specific for plasma kallikrein. Assays for antithrombin III and heparin using S-2222 as the substrate and factor Xa as the enzyme, plasma plasminogen and plasmin inhibitors using S-2251 as the substrate, and plasma prekallikrein and kallikrein inhibitors using Chromozym PK as the substrate have been developed. Synthetic peptides mimicking amino acid sequences adjacent to proteolytic activation cleavage of plasma serine protease precursors appear to be sensitive and relatively specific tools applicable to kinetical and clinical studies of these enzymes and their inhibitors.
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PMID:Serine protease specificity for peptide chromogenic substrates. 14 72

Acetyl-salicylic acid has been found to inhibit the aggregation of erythrocytes and thrombocytes stimulated by proteolytic enzymes (fibrinolysin and trypsin) and phospholipase A. It hampers their hydrolytic action on phospholipids of the blood cells membranes, prevents deformation of the latter under the effect of aggregating agents and also averts a fall of the ATP-ase activity of the erythrocytes membranes caused by parachlormercury-benzoate.
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PMID:[Mechanism of the action of acetylsalicyclic acid on formed element aggregation]. 14 11

The fast-acting and physiologically most important inhibitor of plasmin in human plasma is a recently discovered and purified alpha 2-glycoprotein with a molecular weight of 65,000-70,000 daltons occurring at a concentration of 1 muM. The inhibitor rapidly forms a completely inactive 1:1 stoichometric complex with plasmin through reaction with the B chain (light chain) of the enzyme, which contains the active center. It also reacts with trypsin and very slowly with urokinase and with some other enzymes in purified systems, but its role in vivo as an inhibitor of proteases other than plasmin seems negligible. Antiplasmin is the only plasma protein that can inhibit the fibrinolysis associated with transformed or malignant cells. The plasmin-antiplasmin complex contains neoantigenic structures not present in the parent molecules that may form the basis of immunochemical methods for detecting activation of the fibrinolvtic system in blood.
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PMID:Fast-acting plasmin inhibitor in human plasma. 14 16

Rates of hydrolysis of the newly developed peptide chromogenic substrates S-2160, S-2238, S-2222 and S-2251 and Chromozym TH were tested against highly purified preparations of human plasmin, bovine trypsin, human alpha-thrombin, and bovine factor Xa. S-2160, S-2238, and chromozym TH are sensitive to thrombin, Chromozym TH and S-2238 exhibiting a substantially greater sensitivity than S-2160. All three substrates are insensitive to factor Xa but hydrolyzed to varying degrees by plasmin and trypsin. In contrast, S-2222 is sensitive to factor Xa and insensitive to thrombin. S-2251 is relatively plasmin-specific. In addition, the substrate Chromozym PK was evaluated and found to be relatively specific for plasma kallikrein. Clinically useful assays for antithrombin III and heparin using S-2222 as the substrate and factor Xa as the enzyme, plasma plasminogen and plasmin inhibitors using S-2251 as the substrate, and plasma prekallikrein and kallikrein inhibitors using Chromozym PK as the substrate have been developed.
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PMID:Sensitivity and specificity of plasma serine protease chromogenic substrates. 14 51

Inter-alpha-trypsin inhibitor was isolated from human plasma and submitted to proteolytic degradation by plasmin. A split product of low molecular weight (18 000 daltons) is obtained by gel filtration or solubilisation in perchloric acid. This fragment reacts with an anti-inter-alpha-trypsin inhibitor immune serum and migrates as beta1 globulins. Its specific activity against trypsin (after absorption of residual plasmin on sepharose lysine) was estimated to be 900 mU1/mg. Thus one molecule of fragment can inhibit one molecule of trypsin. As well with native protein as with its fragment, complexes formed with trypsin can be dissociated by urea or sodium dodecyl sulfate. This fragment is similar to the small molecular weight inhibitors obtained directly by solubilisation in perchloric acid from serum, urine and bronchial secretions.
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PMID:[Proteolytic breakdown of human inter-alpha-trypsin inhibitor by plasmin (author's transl)]. 14 41


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