Generation of "neoheparin" from E. coli K5 capsular polysaccharide.
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.
Lindahl
Ulf
U
Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden. ulf.lindahl@imbim.uu.se
Li
Jin-Ping
JP
Kusche-Gullberg
Marion
M
Salmivirta
Markku
M
Alaranta
Sakari
S
Veromaa
Timo
T
Emeis
Jef
J
Roberts
Ian
I
Taylor
Clare
C
Oreste
Pasqua
P
Zoppetti
Giorgio
G
Naggi
Annamaria
A
Torri
Giangiacomo
G
Casu
Benito
B
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
D000925:Anticoagulants; D000991:Antithrombins; D005343:Fibrinolytic Agents; D011135:Polysaccharides, Bacterial; C050673:capsular polysaccharide K5