First Synthetic Carbohydrates with the Full Anticoagulant Properties of Heparin

Petitou, Maurice; Duchaussoy, Philippe; Driguez, Pierre‐Alexandre; Jaurand, Guy; Hérault, Jean-P.; Lormeau, J C; Boeckel, C. A. A. Van; Jm, Herbert

doi:10.1002/(sici)1521-3773(19981116)37:21<3009::aid-anie3009>3.0.co;2-f

Cited by 66 publications

(35 citation statements)

References 7 publications

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“…It is known that heparin binds to antithrombin III (AT III) with changing its conformation, resulting in the inhibition of blood coagulation through complexation with thrombin [3][4][5][6]. In order to clarify the mechanism, many studies have been focused on the modification of functional groups and removal of partial sequence [7][8][9]. Structural requirements for the heparin activity are suggested as the density and precise placement of negative charge, chain flexibility, topological conformation, and average molecular weight [10,11].…”

Section: Introductionmentioning

confidence: 99%

Anticoagulant supramolecular-structured polymers: Synthesis and anti coagulant activity of taurine-conjugated carboxyethylester-polyrotaxanes

Joung

Sengoku

Ooya

et al. 2005

Science and Technology of Advanced Materials

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Polyrotaxanes with both sulfonyl and carboxyl groups were synthesized and characterized for mimicking the anticoagulant activity of heparin. A polyrotaxane consisting of a-cyclodextrins (a-CDs) and poly(ethylene glycol) (PEG) was synthesized, and carboxyethylester (CEE) groups and taurine were successively conjugated with the polyrotaxane to obtain taurine-conjugated carboxyethylester-polyrotaxanes (TAU-CEE-PRxs). The number of a-CDs and the anionic groups could be varied by synthetic conditions. The structural factors of TAU-CEE-PRxs affecting anticoagulant activity were suggested as following: (i) relatively lower threading percentage of a-CDs, (ii) the ratio of anionic groups similar to heparin, and (iii) lower molecular weight of PEG. The TAU-CEE-PRx that sufficiently meet the mentioned requirements showed enhanced antithrombin III (AT III) activity, indicating that the TAU-CEE-PRx interacts with AT III and/or thrombin. From these results, it is suggested that the sliding and rotation of free a-CDs with anionic groups are related with enhancing anticoagulant activity. q

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Section: Introductionmentioning

confidence: 99%

Anticoagulant supramolecular-structured polymers: Synthesis and anti coagulant activity of taurine-conjugated carboxyethylester-polyrotaxanes

Joung

Sengoku

Ooya

et al. 2005

Science and Technology of Advanced Materials

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“…[28] In the second one both domains are present on a single oligosaccharide molecule. [29,30] Thus, SR123781A, [31] a synthetic hexadecasaccharide comprising an ABD and a TBD was obtained from glucose through a convergent synthesis. This heparin mimetic reached phase II-III clinical trials in the prevention of venous thromboembolism (VTE) and in acute coronary syndrome.…”

Section: Longer Oligosaccharidesmentioning

confidence: 99%

Rational Design of Anticoagulant Drugs Using Oligosaccharide Chemistry

Hadri¹,

Petitou²

2011

Chimia

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For a long time, heparin and low molecular weight heparins have been the drugs of choice for the management of thrombosis. Discovery of the antithrombin binding domain in heparin, a critical element in the anticoagulant activity of this polysaccharide, allowed a rational approach based on medicinal carbohydrate chemistry in the design of new anticoagulants. The fully synthetic pentasaccharide fondaparinux that selectively targets blood coagulation factor Xa was first to be developed as a drug. Fondaparinux was followed by various heparin mimicking oligosaccharides prepared with a view to replace polydisperse heparin and low molecular weight heparins by structurally-defined anticoagulants with no unwanted side-effects.

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“…Petitou and coworkers reported the synthesis of hexa, deca-to eicosasaccharide 263→269 IdoA-Glc HP analogs [89,90] "Fig. (38)".…”

Section: Synthesis Of Hp/hs Mimetics As New Antithrombotics Drugsmentioning

confidence: 99%

Recent Chemical and Enzymatic Approaches to the Synthesis of Glycosaminoglycan Oligosaccharides

Karst¹,

Linhardt²

2003

CMC

121

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Glycosaminoglycans, highly charged polycarboxylated, polysulfated polysaccharides, are an important class of therapeutic agents and investigational drug candidates. Heparin has been widely used as a clinical anticoagulant for over 60 years. Low molecular weight heparins have begun to displace heparin and recently a synthetic heparin pentasaccharide was approved for clinical use in Europe. In addition to heparin (and the related heparan sulfate glycosaminoglycan), dermatan sulfate, chondroitin sulfate, hyaluronan and their derivatives are all in various stages of clinical evaluation. This review focuses on the chemical and chemoenzymatic synthesis of glycosaminoglycan oligosaccharides. Recent advances in functional group protection chemistry, conversion of D-gluco to L-ido or D-galacto configurations, glycosylation reactions and the preparation and use of novel starting materials in acidic oligosaccharide synthesis are discussed.

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First Synthetic Carbohydrates with the Full Anticoagulant Properties of Heparin

Cited by 66 publications

References 7 publications

Anticoagulant supramolecular-structured polymers: Synthesis and anti coagulant activity of taurine-conjugated carboxyethylester-polyrotaxanes

Anticoagulant supramolecular-structured polymers: Synthesis and anti coagulant activity of taurine-conjugated carboxyethylester-polyrotaxanes

Rational Design of Anticoagulant Drugs Using Oligosaccharide Chemistry

Recent Chemical and Enzymatic Approaches to the Synthesis of Glycosaminoglycan Oligosaccharides

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