Details

Autor(en) / Beteiligte

• Poupard, Nicolas
• Groult, Hugo
• Bodin, Justine
• Bridiau, Nicolas
• Bordenave-Juchereau, Stéphanie
• Sannier, Frédéric
• Piot, Jean­-Marie
• Fruitier-Arnaudin, Ingrid
• Maugard, Thierry

Titel

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

Ist Teil von

• Carbohydrate polymers, 2017-06, Vol.166, p.156-165

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• •Ultrasonic-assisted radical depolymerization gave LMW-λ-Carrageenan.•Depolymerization associated with glycol splitting helped modulate biological activities.•Lead to interesting heparanase inhibitors with low-anticoagulant properties.•RD-GS-λ-Carrageenan most interesting candidate as potent antiangiogenic.•Same heparanase inhibition as UF-heparin but with no anticoagulant properties. Strongly associated with tumor angiogenesis and metastasis, the enzyme heparanase is an endo-β-d-glucuronidase 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 λ-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 λ-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 λ-carrageenan that displayed major anti-heparanase properties, with an IC50 of 7.32ng/mL and a close-to-zero anticoagulant activity.