Effects of Calcium Ions on the Interactions between Antithrombin and Factor Xa Mediated by Variously Sulfated, Semisynthetic Low-Molecular-Weight Heparins

Claudia Sissi; Lorena Lucatello; Annamaria Naggi; Giangiacomo Torri; Manlio Palumbo

doi:10.1055/s-2002-34304

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2002; 28(4): 355-360
DOI: 10.1055/s-2002-34304

Effects of Calcium Ions on the Interactions between Antithrombin and Factor Xa Mediated by Variously Sulfated, Semisynthetic Low-Molecular-Weight Heparins

Claudia Sissi¹ , Lorena Lucatello¹ , Annamaria Naggi² , Giangiacomo Torri² , Manlio Palumbo¹

¹Department of Pharmaceutical Sciences, University of Padova, Padova, Italy
²Istituto Scientifico di Chimica e Biochimica "G.Ronzoni", Milano, Italy

Abstract

ABSTRACT

A homogeneous set of low-molecular weight heparins, chemically modified to yield different degrees of sulfation, were investigated for their ability to interfere with the antithrombin (AT)-factor Xa (FXa) interaction process in the presence or absence of physiological concentrations of calcium ions. The heparin-AT dissociation constants were not appreciably affected by the presence of the metal ion, whereas the catalytic process was strongly dependent on Ca²⁺. Our data suggest that AT binding to heparin represents the main factor driving the FXa inhibition process. In addition, the presence of the metal ion is likely to mask favorable AT- heparin ionic contacts occurring with the highly sulfated material. These results help in assessing proper structure-activity relationships for glycosaminoglycans, a multitarget family of biologically active compounds.

KEYWORDS

Heparin - factor Xa - antithrombin - sulfation degree - calcium

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Referenzen

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