Heparin-protein interactions antithrombin

Although the order of affinity of PF-4 for different glycosaminogly-cans, and dissociation of their complexes with salts, are typical of nonspecific, electrostatic interactions, PF-4 is not strictly a cationic protein.452 It is probable that heparin binds to clusters of basic amino acids (two lysine pairs) near the carboxyl terminal of a polypeptide chain that has an overall preponderance of acidic amino acid residues.457 High-molecular-weight heparin species can bind two PF-4 molecules, with formation of complexes 10 to 100 times as strong as those with antithrombin.217... 

Based on the mixed-phase method, ACE is introduced for studying the interaction of heparin with the serine protease inhibitors, antithrombin III (ATIII) and secretory leukocyte proteinase inhibitor (SLPI) (85). An etched capillary, to which heparin has been covalently immobilized, was used in this study. This modified capillary both afforded an improvement in the separation of heparin-binding proteins and required a lower quantity of loaded protein. 

Interactions of heparinoids with the most diverse proteins such as enzymes and enzyme inhibitors, cytokines, and adhesion molecules have been described. To date, many more than a hundred heparin binding proteins are known. A number of heparin binding proteins are members of the serpin family of serine protease inhibitors. The best described example is antithrombin [4]. Antithrombin III (AT III) is able to inhibit various serine proteases involved in the blood coagulation process by formation of stable, equimolar complexes. Binding of heparin to AT III accelerates the kinetics of this complex formation by several orders of magnitude. This has been the basis for the successful clinical use of heparin as an anticoagulant for nearly sixty years. 

The indirect thrombin inhibitors are so-named because their antithrombotic effect is exerted by their interaction with a separate protein, antithrombin. Unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the... 

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