Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Poly-L-lysine with molecular masses of 3.3-290 kDa increased the amidolytic activities of leukocyte elastase and cathepsin G at low concentration, but had little effect on the activities of pancreatic elastase, alpha-chymotrypsin, plasmin and thrombin. Highly purified cathepsin G was obtained from column of EAH Sepharose 4B or Suc-L-Tyr-D-Leu-D-Val-pNA-Sepharose (affinity chromatography) by elution with poly-L-lysine solution (0.4 mg/ml, molecular weight (MW.) 290000 or 2.2 mg/ml, MW. 3300). Leukocyte elastase, adsorbed to Suc-L-Tyr-D-Leu-D-Val-pNA-Sepharose, was not eluted with poly-L-lysine solution. The amino acid composition of purified cathepsin G has been determined.
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PMID:Application of poly-L-lysine to purification of leukocyte cathepsin G by affinity chromatography. 139 85

The kinetics of plasminogen activation catalysed by urokinase and tissue-type plasminogen activator were investigated. Kinetic measurements are performed by means of a specific chromogenic peptide substrate for plasmin, D-valyl-L-leucyl-L-lysine 4-nitroanilide. Two methods are proposed for the analysis of the resulting progress curve of nitroaniline formation in terms of zymogen-activation kinetics: a graphical transformation of the parabolic curve and transformation of the curve for nitroaniline production into a linear progress curve by the addition of a specific inhibitor of plasmin, bovine pancreatic trypsin inhibitor. The two methods give similar results, suggesting that the reaction between activator and plasminogen is a simple second-order reaction at least at plasminogen concentrations up to about 10 microM. The kinetics of both Glu1-plasminogen (residues 1-790) and Lys77-plasminogen (residues 77-790) activation were investigated. The results confirm previous observations showing that trans-4-(aminomethyl)cyclohexane-1-carboxylic acid at relatively low concentrations enhances the activation rate of Glu1-plasminogen but not that of Lys77-plasminogen. At higher concentrations both Glu1- and Lys77-plasminogen activation are inhibited. The concentration interval for the inhibition of urokinase-catalysed reactions is shown to be very different from that of the tissue-plasminogen activator system. Evidence is presented indicating that binding to the active site of urokinase (KD = 2.0 mM) is responsible for the inhibition of the urokinase system, binding to the active site of tissue-plasminogen activator is approx. 100-fold weaker, and inhibition of the tissue-plasminogen activator system, when monitored by plasmin activity, is mainly due to plasmin inhibition. Poly-D-lysine (Mr 160 000) causes a marked enhancement of plasminogen activation catalysed by tissue-plasminogen activator but not by urokinase. Bell-shaped curves of enhancement as a function of the logarithm of poly-D-lysine concentration are obtained for both Glu1- and Lys77-plasminogen activation, with a maximal effect at about 10 mg/litre. The enhancement of Glu1-plasminogen activation exerted by trans-4-(aminomethyl)cyclohexane-1-carboxylic acid is additive to that of poly-D-lysine, whereas poly-D-lysine-induced enhancement of Lys77-plasminogen activation is abolished by trans-4-(aminomethyl)cyclohexane-1-carboxylic acid. Analogies are drawn up between the effector functions of poly-D-lysine and fibrin on the catalytic activity of tissue-plasminogen activator.
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PMID:Zymogen-activation kinetics. Modulatory effects of trans-4-(aminomethyl)cyclohexane-1-carboxylic acid and poly-D-lysine on plasminogen activation. 257 38

Poly-L-lysine and certain mixed polymers of L-lysine and other amino acids modify the activity of one- and two-chain tissue-type plasminogen activator (t-PA) towards its substrates. In particular the rate of plasminogen activation in the presence of optimal poly-L-lysine concentrations, is increased by approximately 100-fold. In contrast, activity towards a small synthetic substrate is inhibited by 85%. These effects are observed with both the one- and two-chain forms of t-PA. The use of poly-L-lysines in a coupled assay system optimised for t-PA and plasmin activities allows the reproducible assay of t-PA at the 10(-12) to 10(-13) molar level.
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PMID:Poly-lysines as modifiers of one- and two-chain tissue-type plasminogen activator activity. 309 22

Human peripheral blood monocytes isolated by centrifugation with Mono-Poly resolving medium, and human alveolar macrophages obtained by lung lavage during fiberoscopic bronchoscopy, were cultured in RPMI containing 2% foetal calf serum. The cultures were exposed to modified human proteins: alpha-1-antitrypsin cleaved with papain, fibrinogen degradation products (fraction D) purified from plasmin digest, and non-enzymatically glycosylated (glycated) serum albumin. Conditioned macrophage media were tested for the contents of acute phase cytokines by bioassay with hepatoma cells, and the concentration of interleukin-6 was determined with ELISA. Modified proteins stimulated macrophages to produce acute phase cytokines and the response was not abrogated by polymyxin B in distinction to stimulation of macrophages by endotoxin. Our data indicate that some proteolytically damaged proteins or the end glycosylation products formed in pathological states (acute inflammation, diabetes) may be responsible for the appearance of cytokines in the circulation.
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PMID:Origin of circulating acute phase cytokines: modified proteins may trigger IL-6 production by macrophages. Preliminary report. 804 10

The clinical usefulness of antitumor chemotherapy has been strongly limited by the lack of specificity of most anticancer drugs, which act also against healthy cells. The aim of this work was to design, synthesize, and evaluate a macromolecular prodrug of Cytarabine, a known antitumor drug, which is a specific substrate for plasmin enzyme whose concentration is high in various kinds of tumor mass as a result of plasminogen activator secretion. alpha,beta-Poly(N-hydroxyethyl)-DL-aspartamide (PHEA), a known synthetic and biocompatible polyamino acid, was used as a drug carrier, and Cytarabine was linked to PHEA by D-Val-Leu-Lys spacer synthesized beginning from Cbz-D-Val-LeuOH dipeptide and N6-CbzLys methyl ester. The content of Cytarabine in the purified PHEA-D-Val-Leu-Lys-Cytarabine conjugate was equal to 3% w/w. In vitro experiments in the presence of plasmin evidenced the ability of this enzyme to strongly increase drug release from the macromolecular prodrug, as well as plasma incubation shows high stability of drug-polymer linkage. The direct linkage of Cytarabine to PHEA was also performed and, like PHEA-D-Val-Leu-Lys-Cytarabine conjugate, the obtained PHEA-Cytarabine conjugate showed high stability in plasma, but no release of Cytarabine was revealed in the presence of plasmin.
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PMID:Polymeric prodrug for release of an antitumoral agent by specific enzymes. 1131 74

Thrombus formation remains a serious problem in developing blood compatible materials. Despite continuous, intensive efforts over many years to prepare surfaces that prevent clotting, such surfaces have not been achieved; indeed it seems that surface-induced clotting is inevitable. An alternative approach is to accept that clotting will occur and to design surfaces so that small, nascent clots will be lysed before they can cause harm. The generation of plasmin, as in the fibrinolytic system, may be adopted for this purpose. The vascular endothelium (the inner surface of intact blood vessels) releases nitric oxide (NO) on a continuous basis. NO protects against platelet activation and aggregation, and also has an anti-proliferative effect on smooth muscle cells (SMCs). Based on these two important functions of the vascular system, the approach of constructing a fibrinolytic surface that generates NO is developed in the present work. Poly(oligo(ethylene glycol) methyl ether methacrylate-co-6-amino-2-(2-methacylamido)-hexanoic acid) (poly(OEGMA-co-LysMA)) was attached to a vinyl-functionalized polyurethane (PU) surface by graft polymerization giving a surface (PU-POL) with protein-resistant properties (via poly(OEGMA)) and clot lysing properties (via poly(LysMA)). Selenocystamine, which catalyzes S-nitrosothiol decomposition to generate NO in the vasculature, was then immobilized on the PU-POL surface via covalent attachment. A dual functioning surface with fibrinolytic activity (lysis of nascent clots) and NO releasing ability (inhibition of platelet adhesion and SMC adhesion as well as proliferation) was thereby constructed.
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PMID:A hemocompatible polyurethane surface having dual fibrinolytic and nitric oxide generating functions. 3226 76