Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11:
XN6P4 
]
NCBI PubMed ID: 21484210Journal NLM ID: 8406612Publisher: Springer
Correspondence: linhar
rpi.edu
Institutions: Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA, Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA, The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USA, Division of Medicinal Chemistry and Natural Products, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA
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.
heparin, deacetylation, Heparosan, porcine intestine
Structure type: polymer chemical repeating unit
Location inside paper: p.93, fig.1, K5 heparosan
Trivial name: K5 polysaccharide, K-antigen, N-acetyl heparosan, heparosan (N-acetylheparosan), heparosan, heparosan (glycosaminoglycan GAG), K5 CPS, heparosan (K5-antigen), N-acetylheparosan
Compound class: EPS, K-antigen, CPS, polysaccharide
Contained glycoepitopes: IEDB_115136,IEDB_140630,IEDB_141807,IEDB_151531,IEDB_153764,IEDB_423153
Methods: 1H NMR, de-N-acetylation, enzymatic modification, PAGE, LC-MS, SEC, fermentation, anticoagulation activity, N-sulfonation
NCBI Taxonomy refs (TaxIDs): 562Reference(s) to other database(s): GTC:G26089XS, GlycomeDB:
656
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
report error