کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7789364 | 1500636 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Combinatorial one-pot chemoenzymatic synthesis of heparin
ترجمه فارسی عنوان
سنتز شیمیایی مولکولی ترکیبات ترکیبی هپارین
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Carbohydrate Polymers - Volume 122, 20 May 2015, Pages 399-407
Journal: Carbohydrate Polymers - Volume 122, 20 May 2015, Pages 399-407
نویسندگان
Ujjwal Bhaskar, Guoyun Li, Li Fu, Akihiro Onishi, Mathew Suflita, Jonathan S. Dordick, Robert J. Linhardt,