title: Generation of "neoheparin" from E. coli K5 capsular polysaccharide.
abstract: Heparin remains a major drug in prevention of thromboembolic disease. Concerns related to its animal source have prompted search for heparin analogues. The anticoagulant activity of heparin depends on a specific pentasaccharide sequence that binds antithrombin. We report the generation of a product with antithrombin-binding, anticoagulant, and antithrombotic properties similar to those of heparin, through combined chemical and enzymatic modification of a bacterial (E. coli K5) polysaccharide. The process is readily applicable to large-scale production.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden. ulf.lindahl@imbim.uu.se
authors.forename: Ulf
authors.initials: U
authors.lastname: Lindahl
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Li
authors.forename: Marion
authors.initials: M
authors.lastname: Kusche-Gullberg
authors.forename: Markku
authors.initials: M
authors.lastname: Salmivirta
authors.forename: Sakari
authors.initials: S
authors.lastname: Alaranta
authors.forename: Timo
authors.initials: T
authors.lastname: Veromaa
authors.forename: Jef
authors.initials: J
authors.lastname: Emeis
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
authors.forename: Clare
authors.initials: C
authors.lastname: Taylor
authors.forename: Pasqua
authors.initials: P
authors.lastname: Oreste
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zoppetti
authors.forename: Annamaria
authors.initials: A
authors.lastname: Naggi
authors.forename: Giangiacomo
authors.initials: G
authors.lastname: Torri
authors.forename: Benito
authors.initials: B
authors.lastname: Casu
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000991:Antithrombins / Q000378:metabolism; D016667:Bacterial Capsules; D002240:Carbohydrate Sequence; D004926:Escherichia coli / Q000737:chemistry*; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D020246:Venous Thrombosis / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D005343:Fibrinolytic Agents; D011135:Polysaccharides, Bacterial; C050673:capsular polysaccharide K5