Biomaterial Database

Interaction of reteplase with heparin. A comparison between reteplase and alteplase. 1996

D C Rijken, and A F Jie

Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands.

Reteplase is a protein consisting of the kringle-2 and protease domains of tissue-type plasminogen activator (t-PA). Because intravenous heparin will be used as an adjunct to thrombolytic therapy with reteplase, we investigated the interactions in vitro between heparin and reteplase as well as between heparin and recombinant t-PA (alteplase) as a control. Reteplase and alteplase bound completely to a heparin-agarose column and eluted respectively at 0.39 M and 0.60 M in a NaCl gradient. Two-chain derivatives of reteplase and alteplase eluted at 0.31 M and 0.52 M NaCl respectively. Plasminogen activation by the two-chain derivatives of reteplase and alteplase in a purified system at low ionic strength were stimulated by heparin up to 13- and 22-fold, respectively. However, reteplase required five times more heparin for maximal stimulation than alteplase. In addition, the heparin stimulation of reteplase was more salt sensitive than that of alteplase. In conclusion, both heparin binding and heparin stimulation experiments showed that heparin interacts with reteplase, but the interaction is weaker than with alteplase.

UI	MeSH Term	Description	Entries
D010958	Plasminogen	Precursor of plasmin (FIBRINOLYSIN). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent.	Profibrinolysin,Glu-Plasminogen,Glutamic Acid 1-Plasminogen,Glutamyl Plasminogen,1-Plasminogen, Glutamic Acid,Glu Plasminogen,Glutamic Acid 1 Plasminogen,Plasminogen, Glutamyl
D010959	Tissue Plasminogen Activator	A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases.	Alteplase,Plasminogen Activator, Tissue-Type,T-Plasminogen Activator,Tissue-Type Plasminogen Activator,Actilyse,Activase,Lysatec rt-PA,TTPA,Tisokinase,Tissue Activator D-44,Lysatec rt PA,Lysatec rtPA,Plasminogen Activator, Tissue,Plasminogen Activator, Tissue Type,T Plasminogen Activator,Tissue Activator D 44,Tissue Type Plasminogen Activator
D010960	Plasminogen Activators	A heterogeneous group of proteolytic enzymes that convert PLASMINOGEN to FIBRINOLYSIN. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation.	Extrinsic Plasminogen Activators,Plasminogen Activator,Uterine-Tissue Plasminogen Activator,Uterine Tissue Plasminogen Activator
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005343	Fibrinolytic Agents	Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN.	Antithrombic Drug,Antithrombotic Agent,Antithrombotic Agents,Fibrinolytic Agent,Fibrinolytic Drug,Thrombolytic Agent,Thrombolytic Agents,Thrombolytic Drug,Antithrombic Drugs,Fibrinolytic Drugs,Thrombolytic Drugs,Agent, Antithrombotic,Agent, Fibrinolytic,Agent, Thrombolytic,Agents, Antithrombotic,Drug, Antithrombic,Drug, Fibrinolytic,Drug, Thrombolytic,Drugs, Antithrombic
D006031	Glycosylation	The synthetic chemistry reaction or enzymatic reaction of adding carbohydrate or glycosyl groups. GLYCOSYLTRANSFERASES carry out the enzymatic glycosylation reactions. The spontaneous, non-enzymatic attachment of reducing sugars to free amino groups in proteins, lipids, or nucleic acids is called GLYCATION (see MAILLARD REACTION).	Protein Glycosylation,Glycosylation, Protein
D006493	Heparin	A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.	Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin