title: Toward a biotechnological heparin through combined chemical and enzymatic modification of the Escherichia coli K5 polysaccharide.
abstract: A process to generate glycosaminoglycans with heparin- and heparan sulfate-like sequences from the Escherichia coli K5 capsular polysaccharide is described. This polymer has the same structure as N-acetylheparosan, the precursor in heparin/ heparan sulfate biosynthesis. The process involves chemical N-deacetylation and N-sulfation, enzymatic conversion of up to 60% of the D-glucuronic acid to L-iduronic acid residues, and chemical O-sulfation. Because direct sulfation afforded unwanted 3-O-sulfated (instead of 2-O-sulfated) iduronic acid residues, a strategy involving graded solvolytic desulfation of chemically oversulfated C5-epimerized sulfaminoheparosans was assessed using persulfated heparin and heparan sulfate as model compounds. The O-desulfation process was shown to increase the anti-factor Xa activity of oversulfated heparin.
authors.affiliation: G. Ronzoni Institute for Chemical and Biochemical Research, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Naggi
authors.forename: G
authors.initials: G
authors.lastname: Torri
authors.forename: B
authors.initials: B
authors.lastname: Casu
authors.forename: P
authors.initials: P
authors.lastname: Oreste
authors.forename: G
authors.initials: G
authors.lastname: Zoppetti
authors.forename: J P
authors.initials: JP
authors.lastname: Li
authors.forename: U
authors.initials: U
authors.lastname: Lindahl
mesh_terms: D000818:Animals; D016667:Bacterial Capsules; D001709:Biotechnology; D004926:Escherichia coli / Q000737:chemistry*; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D013431:Sulfates / Q000737:chemistry
chemical_list: D065427:Factor Xa Inhibitors; D011135:Polysaccharides, Bacterial; D013431:Sulfates; C050673:capsular polysaccharide K5; D006493:Heparin; D015951:Factor Xa