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10.1016/j.carbpol.2014.10.054

http://scihub22266oqcxt.onion/10.1016/j.carbpol.2014.10.054
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C4379424!4379424!25817684
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suck abstract from ncbi


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pmid25817684      Carbohydr+Polym 2015 ; 122 (ä): 399-407
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  • Combinatorial one-pot chemoenzymatic synthesis of heparin #MMPMID25817684
  • Bhaskar U; Li G; Fu L; Onishi A; Suflita M; Dordick JS; Linhardt RJ
  • Carbohydr Polym 2015[May]; 122 (ä): 399-407 PMID25817684show ga
  • Contamination in heparin batches during early 2008 has resulted in a significant effort to develop a safer bioengineered heparin using bacterial capsular polysaccharide heparosan and recombinant enzymes derived from the heparin/heparan sulfate biosynthetic pathway. This requires controlled chemical N-deacetylation/ N-sulfonation of heparosan followed by epimerization of most of its glucuronic acid residues to iduronic acid and O-sulfation of the C2 position of iduronic acid and the C3 and C6 positions of the glucosamine residues. A combinatorial study of multi-enzyme, one-pot, in vitro biocatalytic synthesis, carried out in tandem with sensitive analytical techniques, reveals controlled structural changes leading to heparin products similar to animal- derived heparin active pharmaceutical ingredients. Liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy analysis confirms an abundance of heparin?s characteristic trisulfated disaccharide, as well as 3-O-sulfo containing residues critical for heparin binding to antithrombin III and its anticoagulant activity. The bioengineered heparins prepared using this simplified one-pot chemoenzymatic synthesis also show in vitro anticoagulant activity.
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