Biomaterial Database

Active site for heparin cofactor II in low molecular mass dermatan sulfate. Contribution to the antithrombotic activity of fractions with high affinity for heparin cofactor II. 1996

G Mascellani, and L Liverani, and B Parma, and G Bergonzini, and P Bianchini

Opocrin S.p.A. Research and Development Laboratories, Corlo (MO), Italy.

Dermatan sulfate (DS) is currently under clinical investigation as new antithrombotic agent. Unlike heparin, DS does not act through Antithrombin III (ATIII) but primarily through thrombin on Heparin Cofactor II (HCII). HCII is activated by the oversulfated sequence (IdoA2SO3-GalNAc4SO3)4 or by both the sequences (IdoA2SO3-GalNAc4SO3)n and (IdoA-GalNAc-4,6SO3)n, [n > or = 2]. A Low Molecular Mass Dermatan Sulfate (LMM-DS), endowed with a bioavailability three-four times higher than DS, by subcutaneous route, was obtained by chemical depolymerization of DS. The LMM-DS was fractionated by anion exchange and size exclusion chromatography. Fractions with high and low charge densities, high and low molecular masses, and high (2.66) and low (0.07) potencies on HCII were isolated. A relationship between the in vitro HCII-mediated inhibition of thrombin and the chain length of DS fractions containing oversulfated sequences was found [by a multiple regression test]. The in vivo activity increased until it reached a plateau. The important influence on the HCII activity of natural IdoA-GalNAc-4,6SO3 disaccharide was confirmed by investigation on oversulfated DS obtained by a limited and selective chemical 6-O-sulfation in GalNAc4SO3 units of DS.

UI	MeSH Term	Description	Entries
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
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
D002852	Chromatography, Ion Exchange	Separation technique in which the stationary phase consists of ion exchange resins. The resins contain loosely held small ions that easily exchange places with other small ions of like charge present in solutions washed over the resins.	Chromatography, Ion-Exchange,Ion-Exchange Chromatography,Chromatographies, Ion Exchange,Chromatographies, Ion-Exchange,Ion Exchange Chromatographies,Ion Exchange Chromatography,Ion-Exchange Chromatographies
D003871	Dermatan Sulfate	A naturally occurring glycosaminoglycan found mostly in the skin and in connective tissue. It differs from CHONDROITIN SULFATE A (see CHONDROITIN SULFATES) by containing IDURONIC ACID in place of glucuronic acid, its epimer, at carbon atom 5. (from Merck, 12th ed)	Chondroitin Sulfate B,beta-Heparin,Sulfate B, Chondroitin,Sulfate, Dermatan,beta Heparin
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
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D001682	Biological Availability	The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.	Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
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