Fucosylated chondroitin sulfate oligosaccharides exert anticoagulant activity by targeting at intrinsic tenase complex with low FXII activation: Importance of sulfation pattern and molecular size

2017 ◽  
Vol 139 ◽  
pp. 191-200 ◽  
Author(s):  
Junhui Li ◽  
Shan Li ◽  
Lufeng Yan ◽  
Tian Ding ◽  
Robert J. Linhardt ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Anticoagulant Activity ◽  
Molecular Size ◽  
Sulfation Pattern

Glycosaminoglycans from growing antlers of wapiti (Cervus elaphus)

1997 ◽  
Vol 77 (4) ◽  
pp. 715-721 ◽  
Author(s):  
H. H. Sunwoo ◽  
L. Y. M. Sim ◽  
T. Nakano ◽  
R. J. Hudson ◽  
J. S. Sim
Keyword(s):  
Hyaluronic Acid ◽  
Chondroitin Sulfate ◽  
Cervus Elaphus ◽  
Molecular Size ◽  
Enzymatic Digestion ◽  
Gel Chromatography ◽  
Cellulose Acetate Electrophoresis ◽  
Cartilaginous Tissues ◽  
Chondroitin Sulfates ◽  
Velvet Antler

The emerging wapiti industry in North America is based largely on markets for velvet antlers which are used in oriental medicine. Despite the economic opportunity, enthusiasm has been dampened by incomplete understanding of the chemical and pharmacological properties of velvet antler. This study characterizes polysaccharide constituents of glycosaminoglycans in growing antler of wapiti (Cervus elaphus). Glycosaminoglycans were isolated from four sections (tip, upper, middle and base) of growing antlers, and were studied using cellulose acetate electrophoresis, gel electrophoresis, enzymatic digestion and gel chromatography. The tip and upper sections of the antler which are rich in cartilaginous tissues contained chondroitin sulfate as a major glycosaminoglycan with small amounts of hyaluronic acid. In the middle and base sections containing bone and bone marrow, chondroitin sulfate was also a major glycosaminoglycan with small amounts of hyaluronic acid and chondroitinase-ACI resistant materials. More than half of chondroitin sulfate from the middle and base sections had larger molecular size than did the chondroitin sulfates from the tip and upper sections. Key words: Glycosaminoglycans, chondroitin sulfate, antler, wapiti

scholarly journals A Study for the Access to a Semi-synthetic Regioisomer of Natural Fucosylated Chondroitin Sulfate with Fucosyl Branches on N-acetyl-Galactosamine Units

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 655 ◽  
Author(s):  
Giulia Vessella ◽  
Serena Traboni ◽  
Anna V. A. Pirozzi ◽  
Antonio Laezza ◽  
Alfonso Iadonisi ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Anticoagulant Activity ◽  
The Body ◽  
New Drugs ◽  
Coagulation Cascade ◽  
Drug Candidate ◽  
Heterogeneous Structure ◽  
Anticoagulant Drug ◽  
Chemical Strategy

Fucosylated chondroitin sulfate (fCS) is a glycosaminoglycan found up to now exclusively in the body wall of sea cucumbers. It shows several interesting activities, with the anticoagulant and antithrombotic as the most attractive ones. Its different mechanism of action on the blood coagulation cascade with respect to heparin and the retention of its activity by oral administration make fCS a very promising anticoagulant drug candidate for heparin replacement. Nonetheless, its typically heterogeneous structure, the detection of some adverse effects and the preference for new drugs not sourced from animal tissues, explain how mandatory is to open an access to safer and less heterogeneous non-natural fCS species. Here we contribute to this aim by investigating a suitable chemical strategy to obtain a regioisomer of the natural fCS polysaccharide, with sulfated l-fucosyl branches placed at position O-6 of N-acetyl-d-galactosamine (GalNAc) units instead of O-3 of d-glucuronic acid (GlcA) ones, as in natural fCSs. This strategy is based on the structural modification of a microbial sourced chondroitin polysaccharide by regioselective insertion of fucosyl branches and sulfate groups on its polymeric structure. A preliminary in vitro evaluation of the anticoagulant activity of three of such semi-synthetic fCS analogues is also reported.

Fucosylated Chondroitin Sulfate 9–18 Oligomers Exhibit Molecular Size-Independent Antithrombotic Activity while Circulating in the Blood

2020 ◽  
Vol 15 (8) ◽  
pp. 2232-2246 ◽  
Author(s):  
Lufeng Yan ◽  
Danli Wang ◽  
Yanlei Yu ◽  
Fuming Zhang ◽  
Xingqian Ye ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Molecular Size ◽  
Antithrombotic Activity

Serpin-independent anticoagulant activity of a fucosylated chondroitin sulfate

2008 ◽  
Vol 100 (09) ◽  
pp. 420-428 ◽  
Author(s):  
Bianca F. Glauser ◽  
Mariana S. Pereira ◽  
Robson Q. Monteiro ◽  
Paulo A. S. Mourão
Keyword(s):  
Chondroitin Sulfate ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Anticoagulant Effect ◽  
Coagulation System ◽  
Heparin Cofactor Ii ◽  
Thrombin Inhibition ◽  
Coagulation Proteins ◽  
Dependent Inhibition ◽  
Structure Versus

SummaryFucosylated chondroitin sulfate is a glycosaminoglycan from sea cucumber composed of a chondroitin sulfate-like core with branches of sulfated fucose. This glycosaminoglycan has high anticoagulant and antithrombotic activities. Its serpin-dependent anticoagulant activity is mostly due to activating thrombin inhibition by heparin cofactor II. Here, we evaluated the anticoagulant activity of fucosylated chondroitin sulfate using antithrom-bin- and heparin cofactor II-free plasmas. In contrast to mammalian heparin, the invertebrate glycosaminoglycan is still able to prolong coagulation time and delay thrombin and factor Xa generation in serpin-free plasmas. These observations suggest that fucosylated chondroitin sulfate has a serpin-independent anticoagulant effect. We further investigated this effect using purified blood coagulation proteins. Clearly, fucosylated chondroitin sulfate inhibits the intrinsic tenase and prothrombinase complexes, which are critical for thrombin generation. It is possiblethat the invertebrate chondroitin sulfate inhibits interactions between cofactor Va and factor Xa. We also employed chemically modified polysaccharides in order to trace a structure versus activity relationship. Removal of the sulfated fucose branches, but not reduction of the glucuronic acid residues to glucose, abolished its activity. In conclusion, fucosylated chondroitin sulfate has broader effects on the coagulation system than mammalian glycosaminoglycans. In addition to its serpin-dependent inhibition of coagulation protease, it also inhibits the generation of factor Xa and thrombin by the tenase and prothrombinase complexes, respectively. In plasma systems, the serpin-independent anticoagulant effect of fucosylated chondroitin sulfate predominates over its serpin-dependent action. This glycosaminoglycan opens new avenues for the development of antithrombotic agents.

Structure and haemostatic effects of generic versions of enoxaparin available for clinical use in Brazil: Similarity to the original drug

2012 ◽  
Vol 107 (02) ◽  
pp. 302-314 ◽  
Author(s):  
Bianca Glauser ◽  
Bruno Vairo ◽  
Stephan-Nicollas Oliveira ◽  
Leonardo Cinelli ◽  
Mariana Pereira ◽  
...  
Keyword(s):  
Size Distribution ◽  
Active Ingredient ◽  
Patent Protection ◽  
Anticoagulant Activity ◽  
Therapeutic Option ◽  
Minor Component ◽  
Molecular Size ◽  
Pharmaceutical Products ◽  
Clinical Use ◽  
Molecular Size Distribution

SummaryPatent protection for enoxaparin has expired. Generic preparations are developed and approved for clinical use in different countries. However, there is still skepticism about the possibility of making an exact copy of the original drug due to the complex processes involved in generating low-molecular-weight heparins. We have undertaken a careful analysis of generic versions of enoxaparin available for clinical use in Brazil. Thirty-three batches of active ingredient and 70 of the final pharmaceutical product were obtained from six different suppliers. They were analysed for their chemical composition, molecular size distribution, in vitro anticoagulant activity and pharmacological effects on animal models of experimental thrombosis and bleeding. Clearly, the generic versions of enoxaparin available for clinical use in Brazil are similar to the original drug. Only three out of 33 batches of active ingredient from one supplier showed differences in molecular size distribution, resulting from a low percentage of tetrasaccharide or the presence of a minor component eluted as monosaccharide. Three out of 70 batches of the final pharmaceutical products contained lower amounts of the active ingredient than that declared by the suppliers. Our results suggest that the generic versions of enoxaparin are a viable therapeutic option, but their use requires strict regulations to ensure accurate standards.

scholarly journals Structure and Anticoagulant Activity of a Fucosylated Chondroitin Sulfate from Echinoderm

1996 ◽  
Vol 271 (39) ◽  
pp. 23973-23984 ◽  
Author(s):  
Paulo A. S. Mourão ◽  
Mariana S. Pereira ◽  
Mauro S. G. Pavão ◽  
Barbara Mulloy ◽  
Douglas M. Tollefsen ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Anticoagulant Activity
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