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Control of the heparosan N-deacetylation leads to an improved bioengineered heparin.
- Source :
-
Applied Microbiology & Biotechnology . Jul2011, Vol. 91 Issue 1, p91-99. 9p. - Publication Year :
- 2011
-
Abstract
- The production of the anticoagulant drug heparin from non-animal sources has a number of advantages over the current commercial production of heparin. These advantages include better source material availability, improved quality control, and reduced concerns about animal virus or prion impurities. A bioengineered heparin would have to be chemically and biologically equivalent to be substituted for animal-sourced heparin as a pharmaceutical. In an effort to produce bioengineered heparin that more closely resembles pharmaceutical heparin, we have investigated a key step in the process involving the N-deacetylation of heparosan. The extent of N-deacetylation directly affects the N-acetyl/ N-sulfo ratio in bioengineered heparin and also impacts its molecular weight. Previous studies have demonstrated that the presence and quantity of N-acetylglucosamine in the nascent glycosaminoglycan chain, serving as the substrate for the subsequent enzymatic modifications (C5 epimerization and O-sulfonation), can impact the action of these enzymes and, thus, the content and distribution of iduronic acid and O-sulfo groups. In this study, we control the N-deacetylation of heparosan to produce a bioengineered heparin with an N-acetyl/ N-sulfo ratio and molecular weight that is similar to animal-sourced pharmaceutical heparin. The structural composition and anticoagulant activity of the resultant bioengineered heparin was extensively characterized and compared to pharmaceutical heparin obtained from porcine intestinal mucosa. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BIOENGINEERING
*HEPARIN
*ANTICOAGULANTS
*GLYCOSAMINOGLYCANS
*SULFONATION
Subjects
Details
- Language :
- English
- ISSN :
- 01757598
- Volume :
- 91
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Applied Microbiology & Biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 61212186
- Full Text :
- https://doi.org/10.1007/s00253-011-3231-5