Heparin and low molecular weight heparins as scaffolds for assembling antithrombin and serine proteases.

摘要

In a recent issue of Thrombosis Research, Wagen-voord and his collaborators have made important contributions to our current understanding on how heparin fragments with high affinity for antithrom-bin (AT) express their catalytic actions on AT-mediated inactivation of thrombin and factor Xa [1]. Key aspects of this contribution by Wagenvoord et al. include: the rather large series of well defined molecular species of heparin (52 in all) they used to measure the affinities of factor Xa and thrombin for the various species of heparins with high affinity for AT; the observations that the fragments of heparin that are able to bind thrombin and/or factor Xa have significantly higher affinities for thrombin than for factor Xa; and the observations that within certain limits, the concentration-dependent catalytic activity of AT-binding heparin fractions on the inactivation of factor Xa decreases when the molecular weights of heparin fragments exceed 10,000. Another novel conclusion in this study is the view that the rate at which thrombin is inactivated by AT-heparin per high affinity pentasaccharide with a C-domain is independent of the molecular weight of the heparin fragment. The dissociation constants that describe the affinities of thrombin and factor Xa for heparin fragments bound to AT and reported in this study are very similar to those reported by Jordan et al.