Production of heparin and λ-carrageenan anti-heparanase derivatives using a combination of physicochemical depolymerization and glycol splitting

Strongly associated with tumor angiogenesis and metastasis, the enzyme heparanase is an endo-beta-Dglucuronidase which is overexpressed in the tumor microenvironment. Its inhibition could be one of the most promising anti-angiogenic approaches to date. Although heparin is known as a good heparanase inhibitor, it also possesses major anticoagulant properties that may be incompatible with its use as an anti-angiogenic agent, hence the considerable interest for other sources of sulfated polysaccharides. Recent investigations point to lambda-carrageenans, highly sulfated galactans with a tremendous potential that are found in red algae. This study describes the production of low-molecular-weight (LMW) heparins and lambda-carrageenans, using a combination of glycol splitting and ultrasonically-assisted radical hydrolysis using hydrogen peroxide. The structural characteristics, as well as the anticoagulant and antiheparanase activities of the resulting products were assessed. The best candidate was a LMW glycol-split lambda-carrageenan that displayed major anti-heparanase properties, with an IC50 of 7.32 ng/mL and a close-to-zero anticoagulant activity. (C) 2017 Elsevier Ltd. All rights reserved.