BIOMAT Database Logo BIOMAT Database Logo

Structure-activity relationship in heparin: a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity. 1983

J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti

The structures of the tetrasaccharide (beta-D-glucuronic acid)1 leads to 4 (N-sulfate-3,6-di-0-sulfate-alpha-D-glucosamine)1 leads to 4(2-0-sulfate-alpha-L-iduronic acid)1 leads to 4(N-sulfate-6-0-sulfate-D-glucosamine) and of the pentasaccharide (N-sulfate-6-0-sulfate-alpha-D-glucosamine)1 leads to 4(beta-D-glucuronic acid)1 leads to 4(N-sulfate-3,6-di-0-sulfate-alpha-D-glucosamine)1 leads to 4(2-0-sulfate-alpha-L-iduronic acid)1 leads to 4(N-sulfate-6-0-sulfate-D-glucosamine), both prepared for the first time, by chemical synthesis from D-glucose and D-glucosamine, have been confirmed by nuclear magnetic resonance. The synthetic tetrasaccharide neither binds to AT-III nor induces anti-factor Xa activity enhancement of this inhibitor. In contrast, the synthetic pentasaccharide strongly binds to AT-III (Ka: 7.10(6)M-1) forming an equimolar complex and also enhances the AT-III inhibitory activity towards factor Xa. These results confirm that the synthetic pentasaccharide with the above structure corresponds to the actual minimal sequence required in heparin for binding to AT-III.

UI MeSH Term Description Entries
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D002850 Chromatography, Gel Chromatography on non-ionic gels without regard to the mechanism of solute discrimination. Chromatography, Exclusion,Chromatography, Gel Permeation,Chromatography, Molecular Sieve,Gel Filtration,Gel Filtration Chromatography,Chromatography, Size Exclusion,Exclusion Chromatography,Gel Chromatography,Gel Permeation Chromatography,Molecular Sieve Chromatography,Chromatography, Gel Filtration,Exclusion Chromatography, Size,Filtration Chromatography, Gel,Filtration, Gel,Sieve Chromatography, Molecular,Size Exclusion Chromatography
D005170 Factor X Storage-stable glycoprotein blood coagulation factor that can be activated to factor Xa by both the intrinsic and extrinsic pathways. A deficiency of factor X, sometimes called Stuart-Prower factor deficiency, may lead to a systemic coagulation disorder. Autoprothrombin III,Coagulation Factor X,Stuart Factor,Stuart-Prower Factor,Blood Coagulation Factor X,Factor 10,Factor Ten,Stuart Prower Factor,Factor X, Coagulation
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000990 Antithrombin III A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily. Heparin Cofactor I,Antithrombin III-Alpha,Atenativ,Heparin Co-Factor I,Kybernin,Serpin C1,Thrombate III,Antithrombin III Alpha,Antithrombin IIIAlpha,Cofactor I, Heparin,Heparin Co Factor I
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015951 Factor Xa Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors. Autoprothrombin C,Coagulation Factor Xa,Factor X, Activated,Thrombokinase,Activated Factor X,Blood Coagulation Factor X, Activated,Factor 10A,Factor Ten A,Factor Xa, Coagulation

Related Publications

J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti
Antithrombotic effects of synthetic pentasaccharide with high affinity for plasma antithrombin III in non-human primates.
October 1993, Thrombosis and haemostasis,
J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti
Examination, by 1H-n.m.r. spectroscopy, of the binding of a synthetic, high-affinity heparin pentasaccharide to human antithrombin III.
January 1989, Carbohydrate research,
J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti
Proceedings: The relationship between antithrombin III, progressive antithrombin activity and anti Xa activity in plasma.
September 1975, Thrombosis et diathesis haemorrhagica,
J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti
Sequence variation in heparin octasaccharides with high affinity for antithrombin III.
November 1984, Biochemistry,
J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti
Antithrombin III "Northwick Park": a variant antithrombin with normal affinity for heparin but reduced heparin cofactor activity.
June 1985, Thrombosis and haemostasis,
J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti
Interaction of factor Xa with heparin does not contribute to the inhibition of factor Xa by antithrombin III-heparin.
October 1990, Biochemistry,
J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti
Conformation of heparin pentasaccharide bound to antithrombin III.
October 2001, The Biochemical journal,
J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti
Inhibition of factor X and factor V activation by dermatan sulfate and a pentasaccharide with high affinity for antithrombin III in human plasma.
October 1990, European journal of biochemistry,
J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti
An investigation of the functional role of the carboxylic groups of heparin. Affinity for antithrombin III and anti-Xa activity of selectively carboxyl esterified heparin.
January 1985, Seminars in thrombosis and hemostasis,
J Choay, and M Petitou, and J C Lormeau, and P Sinaÿ, and B Casu, and G Gatti
Heparinase I acts on a synthetic heparin pentasaccharide corresponding to the antithrombin III binding site.
December 2000, Thrombosis research,
Copied contents to your clipboard!