Rensselaer Polytechnic Institute

Makoto Hirakane

Jonathan S Dordick

Robert J Linhardt

Kevin Li

Li Fu

Daisuke Mori

Trevor John Simmons

Navdeep Grover

Payel Datta

Elena Paskaleva

Lei Lin

Paul Brodfuehrer

Akihiro Onishi

Marc Douaisi

The present disclosure relates to synthesis of heparin, which may be bioequivalent to porcine USP Heparin Sodium. The synthesis may involve three intermediates starting from heparosan.

Biosynthetic heparin

A heparin structure with increased anticoagulant activity and method of making the same are disclosed. A heparin sample is provided and treated with a heparan sulfate sulfotransferase in an enzymatic reaction to add sulfuryl groups from a sulfuryl group source to the heparin sample, resulting in a heparin structure having above about 8% more 3-O-sulfo groups relative to wild-type bovine intestinal heparin. The added sulfuryl groups modify the heparin structure and increase the sample's binding to antithrombin III and its anticoagulant activity to be more similar and a viable alternative to porcine intestinal heparin. The modified heparin exhibits an anti-FXa activity and an anti-FIIa activity greater than about 180 U/mg, and a ratio of the anti-FXa activity to the anti-FIIa activity of about 0.9 to about 1.1, consistent with U.S. Pharmacopeia (USP) heparin activity specifications.

Enzymatic preparation of increased anticoagulant bovine sourced heparin

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Rensselaer, NY, United States of America

Makoto Hirakane