Comparison of Low-Molecular-Weight Heparins Prepared From Bovine Heparins With Enoxaparin

Abstract

Heparin and its low-molecular-weight heparin (LMWH) derivatives are widely used clinical anticoagulants. These drugs are critical for the practice of medicine in applications including kidney dialysis, cardiopulmonary bypass, and in the management of venous thromboembolism. Currently, these drugs are derived from livestock, primarily porcine intestine. The worldwide dependence on a single animal species has made the supply chain for this critical drug quite fragile, leading to the search for other sources of these drugs, including bovine tissues such as bovine intestine or lung. A number of laboratories are currently examining the similarities and differences between heparins prepared from porcine and bovine tissues. The current study is designed to compare LMWH prepared from bovine heparins through chemical β-elimination, a process currently used to prepare the LMWH, enoxaparin, from porcine heparin. Using top-down, bottom-up, compositional analysis and bioassays, LMWHs, derived from bovine lung and intestine, are shown to closely resemble enoxaparin.

Expedient Synthesis of Core Disaccharide Building Blocks from Natural Polysaccharides for Heparan Sulfate Oligosaccharide Assembly

“…$14 g À1 ) and produced on al arge scale for pharmaceutical use.W e envisioned that key IdoA-containing building blocks for HS/ heparin synthesis might be obtained through the controlled hydrolysis of heparin. However,h ydrolysis of heparin under basic conditions results in b-elimination to form unsaturated uronic acid moieties, [5] while nitrous acid mediated depolymerization of heparin is accompanied by deaminative ring contraction of GlcN. [6] Fortunately,elegant studies by Davidson and Meyer, [7] as well as Lopin and Jacquinet, [8] showed that chondroitin sulfate (CS) could be hydrolyzed using aqueous H 2 SO 4 to provide GlcA-N-acetylgalactosamine (GalNAc) disaccharides.S elective cleavage of the GalNAcÀ GlcA bond was presumably facilitated by neighboring group participation from the N-acetyl group of GalNAc.…”

Expedient Synthesis of Core Disaccharide Building Blocks from Natural Polysaccharides for Heparan Sulfate Oligosaccharide Assembly

“…We envisioned that key IdoA‐containing building blocks for HS/heparin synthesis might be obtained through the controlled hydrolysis of heparin. However, hydrolysis of heparin under basic conditions results in β‐elimination to form unsaturated uronic acid moieties, while nitrous acid mediated depolymerization of heparin is accompanied by deaminative ring contraction of GlcN . Fortunately, elegant studies by Davidson and Meyer, as well as Lopin and Jacquinet, showed that chondroitin sulfate (CS) could be hydrolyzed using aqueous H 2 SO 4 to provide GlcA‐ N ‐acetylgalactosamine (GalNAc) disaccharides.…”

Structure-based engineering of heparinase I with improved specific activity for degrading heparin

“…The use of nitrite in the lysis process has caused serious environmental pollution, and the drug activity of prepared LMWHs is low. However, LMWH production still requires the use of chemical degradation instead of purely enzymatic degradation due to the low production and activity of enzymes [35]. Natural HepI is mainly produced by Pedobacter heparinus [36].…”