Mechanism of thrombin inactivation by immobilized heparin.
The ability of heparin to interact with plasma proteins, in particular antithrombin III (ATIII) and thrombin, is its primary mechanism as an anticoagulant drug. Research efforts have focused on the biological activity of heparin under three conditions: in solution as a free molecule, chemically coupled directly onto a polymer surface, and coupled onto a polymer surface using hydrophilic spacer groups. Each of these conditions yields altered biological activity, presumably a result of differing binding interactions with ATIII and thrombin. In this report, insights into binding interaction of direct versus polyethylene oxide space immobilized heparin with ATIII, thrombin, and the generation of the thrombin-antithrombin complex will be presented.
Byun
Y
Y
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City 84132, USA.
Jacobs
H A
HA
Kim
S W
SW
D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D000990:Antithrombin III / Q000737:chemistry; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D011092:Polyethylene Glycols; D013499:Surface Properties; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D011092:Polyethylene Glycols; D000990:Antithrombin III; D006493:Heparin; D013917:Thrombin