Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme
Article Abstract:
The sulphated polysaccharide heparin is synthesized by connective-tissue-type mast cells. Endogenous heparin is not present in the blood, and as such has not physiological role in regulating blood coagulation. The biosynthesis of heparin reveals a range of enzymatic reactions, such as sulphation at certain positions. The initial modification step catalyzed by N-deacetylase/N-sulphotransferase-2 (NDST-2) is required for subsequent reactions. Mice with a targeted disruption of the gene encoding NDST-2 cannot synthesize sulphated heparin.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1999
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Synthesis of thrombin-inhibiting heparin mimetics without side effects
Article Abstract:
The complex structure of the polysaccharide heparin has limited fragmentation resulting in better-tolerated heparin preparations of low molecular mass. However heparin-induced thrombocytopaenia (HIT) linked to platelet factor 4 (PF4) is still a significant side effect of heparinotherapy. The total synthesis of the pentasaccharide anti-thrombin-binding site of heparin has been possible, representing a new group of potential antithrombotic drugs. A multistep converging synthesis to yield sulphated oligosaccharides is presented.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1999
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Sugars slide into heparin activity
Article Abstract:
Petitou and colleagues have designed and chemically synthesized a complex oligosaccharide with more potency that standard heparin and low-molecular-weight heparin. They combined three identical disaccharide units to provide a regular hexasaccharide having just one type of uronic acid. The heavily sulphated structure can also bind to thrombin and the result is a heptadecassaccharide containing a simplified pentasacchardie A-domain.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1999
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