title: Production of heparin and λ-carrageenan anti-heparanase derivatives using a combination of physicochemical depolymerization and glycol splitting.
abstract: 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 IC50of 7.32ng/mL and a close-to-zero anticoagulant activity.
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSs, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042, La Rochelle, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Poupard
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSs, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042, La Rochelle, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Groult
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSs, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042, La Rochelle, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Bodin
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSs, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042, La Rochelle, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bridiau
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSs, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042, La Rochelle, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bordenave-Juchereau
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSs, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042, La Rochelle, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sannier
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSs, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042, La Rochelle, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Piot
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSs, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042, La Rochelle, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fruitier-Arnaudin
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSs, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042, La Rochelle, France. Electronic address: tmaugard@univ-lr.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Maugard
mesh_terms: D002351:Carrageenan / Q000737:chemistry*; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D006018:Glycols; D006493:Heparin / Q000737:chemistry*; D000099175:Heparanase
chemical_list: D002351:Carrageenan; D005966:Glucuronidase; D006018:Glycols; D006493:Heparin; D000099175:Heparanase
keywords: Angiogenesis; Carrageenan; Depolymerization; Glycol split; Heparanase; Heparin