Structure-activity relationship of antithrombotic polysaccharide derivatives. 1995

G Franz, and S Alban
University of Regensburg, Germany.

Heparin has been the drug of choice in clinical pre-surgical and post-surgical prophylaxis of thrombotic events. However, because of its side-effects, such as bleeding and other disadvantages (i.e. chemical inhomogeneity and variability of its physiological activities), alternatives to heparin are an important field of research. A necessary procedure in the development of new drugs is the evaluation of structure-activity relationships. Genuine neutral polysaccharides were chemically modified and examined for their anticoagulant activities. The linear beta-1,3-glucan curdlan, an easily available bacterial polysaccharide, served as the basic polymer. It could be established that the anticoagulant activity was dependent on the degree of sulfation and the molecular weight. For heparin, the sulfation pattern, i.e. the actual location of the sulfate groups along the heparin chain, was of importance in addition to the degree of sulfation. Therefore, we investigated whether there was also a relationship between the substitution pattern of the curdlan sulfates and their anticoagulant activity. For determination of the substitution pattern of the sulfated polysaccharides, a method was developed that is based on synthesis of the partially alkylated alditol acetates of the polymer and examination of these derivatives using combined gas chromatography-mass spectrometry. In addition to the analytical data, the structure-activity relationship of anticoagulative curdlan sulfates is presented.

UI MeSH Term Description Entries
D008401 Gas Chromatography-Mass Spectrometry A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds. Chromatography, Gas-Liquid-Mass Spectrometry,Chromatography, Gas-Mass Spectrometry,GCMS,Spectrometry, Mass-Gas Chromatography,Spectrum Analysis, Mass-Gas Chromatography,Gas-Liquid Chromatography-Mass Spectrometry,Mass Spectrometry-Gas Chromatography,Chromatography, Gas Liquid Mass Spectrometry,Chromatography, Gas Mass Spectrometry,Chromatography, Mass Spectrometry-Gas,Chromatography-Mass Spectrometry, Gas,Chromatography-Mass Spectrometry, Gas-Liquid,Gas Chromatography Mass Spectrometry,Gas Liquid Chromatography Mass Spectrometry,Mass Spectrometry Gas Chromatography,Spectrometries, Mass-Gas Chromatography,Spectrometry, Gas Chromatography-Mass,Spectrometry, Gas-Liquid Chromatography-Mass,Spectrometry, Mass Gas Chromatography,Spectrometry-Gas Chromatography, Mass,Spectrum Analysis, Mass Gas Chromatography
D008745 Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed) Methylations
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D009389 Neovascularization, Pathologic A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions. Angiogenesis, Pathologic,Angiogenesis, Pathological,Neovascularization, Pathological,Pathologic Angiogenesis,Pathologic Neovascularization,Pathological Angiogenesis,Pathological Neovascularization
D011134 Polysaccharides Long chain polymeric CARBOHYDRATES composed of MONOSACCHARIDES linked by glycosidic bonds. Glycan,Glycans,Polysaccharide
D001780 Blood Coagulation Tests Laboratory tests for evaluating the individual's clotting mechanism. Coagulation Tests, Blood,Tests, Blood Coagulation,Blood Coagulation Test,Coagulation Test, Blood,Test, Blood Coagulation
D004126 Dimethylformamide A formamide in which the amino hydrogens are replaced by methyl groups. N,N-Dimethylformamide,N,N Dimethylformamide
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
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
D005936 Glucans Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. Glucan,Polyglucose,Polyglucoses,Glucan (BO),Glucose Polymer,Polycose,Polymer, Glucose

Related Publications

G Franz, and S Alban
December 2016, Future medicinal chemistry,
G Franz, and S Alban
June 2017, Anticancer research,
G Franz, and S Alban
November 1971, Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
G Franz, and S Alban
September 1965, Archives internationales de pharmacodynamie et de therapie,
G Franz, and S Alban
December 1983, Zhongguo yao li xue bao = Acta pharmacologica Sinica,
G Franz, and S Alban
October 1980, Psychopharmacology bulletin,
G Franz, and S Alban
March 2014, Marine drugs,
G Franz, and S Alban
August 1985, Il Farmaco; edizione scientifica,
G Franz, and S Alban
January 1986, Drugs under experimental and clinical research,
Copied contents to your clipboard!