Highly Sulfated Dermatan Sulfates from Ascidians

• Published in: The Journal of biological chemistry 1998-10, Vol.273 (43), p.27848-27857
• Main Authors: Pavão, Mauro S.G., Aiello, Karin R.M., Werneck, Claudio C., Silva, Luiz Claudio F., Valente, Ana-Paula, Mulloy, Barbara, Colwell, Niall S., Tollefsen, Douglas M., Mourão, Paulo A.S.
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.43.27848

Dermatan sulfates with the same backbone structure [4-α-l-IdceA-1→3-β-d-GalNAc-1]nbut with different patterns of sulfation substitutions have been isolated from the ascidian body. All the ascidian dermatan sulfates have a high content of 2-O-sulfated α-l-iduronic acid residues but differ in the pattern of sulfation of the N-acetyl-β-d-galactosamine units. Styela plicata and Halocynthia pyriformis have 4-O-sulfated units, but in Ascidian nigra they are 6-O-sulfated. This collection of ascidian dermatan sulfates (together with native and oversulfated mammalian dermatan sulfate), where the extent and position of sulfate substitution have been fully characterized, were tested in anticoagulant assays. Dermatan sulfate from A. nigra has no discernible anticoagulant activity, which indicates that 4-O-sulfation of theN-acetyl-β-d-galactosamine is essential for the anticoagulant activity of this glycosaminoglycan. In contrast dermatan sulfates from S. plicata and H. pyriformis are potent anticoagulants due to potentiation of thrombin inhibition by heparin cofactor II. These ascidian dermatan sulfates have ∼10-fold and ∼6-fold higher activity with heparin cofactor II than native and an oversulfated mammalian dermatan sulfate, respectively. They have no effect on thrombin or factor Xa inhibition by antithrombin. These naturally oversulfated ascidian dermatan sulfates are sulfated at selected sites required for interaction with heparin cofactor II and thus have specific and potent anticoagulant activity.