Low anticoagulant heparin (LAH)

 
Heparin is involved in many key biological protein interactions. This means that heparin derivatives are considered potential new drugs that could be used in as diverse medical conditions as cancer, viral infections, inflammation, malaria, Alzheimer’s, Crohn’s disease, asthma, cystic fibrosis and others1. The vast unexploited therapeutic potential of this molecule is mainly due to the structural complexity and heterogeneity. For use in alternative treatments the strong anticoagulant properties are undesirable. One way of removing the anticoagulant activity is by chemically splitting the pentasaccharide sequence (as seen in Fondaparinux) responsible for binding to antithrombin. More specifically this can be done by an oxidative glycol split using periodate followed by reducing the aldehyde moieties generated with borohydride (scheme 1). The thus formed modified polysaccharide chain can be hydrolysed under mild acidic conditions to yield shorter sequences with better medicinal effects2. Such LAHs, like Sevuparin, are currently being developed to treat malaria and sickle-cell disease.
 
 
Scheme 1: Schematic structure of low anticoagulant heparin (LAH)
 
 
Another approach involves reducing/removing the number of sulfate groups in heparin. One such method is currently being developed to create 2O-, 3O-desulfated heparin (ODSH) for treating chemotherapy-induced thrombocytopenia3.
 
REFERENCES
 
1. Heparin and Related Drugs: Beyond Anticoagulant Activity, Clive Page (http://dx.doi.org/10.1155/2013/910743).
2. Patent no. US 2015/0031638 A1. Dilaforette AB, issued Jan. 29, 2015. 
3. Patent no. US 8,734,804 B2. Cantex Pharmaceuticals, inc. May 27, 2014