Antithrombin-binding oligosaccharide

Although anionic density appears to be a necessary condition for anticoagulancy, it is not sufficient, since chains which lack an antithrombin-binding oligosaccharide sequence show little or no anticoagulant activity. Just as clearly, antithrombin binding itself is not a sufficient condition, since these sequences show no anticoagulant activity themselves. 

Structural variants in structure 11 appear compatible with high-affin-ity binding to antithrombin. Thus, the acetoxyl group of residue ANA6S could be removed (by hydrazinolysis) and replaced by a sulfate group without loss of affinity.172 Natural, high-affinity oligosaccharides con-... 

Antithrombin, already mentioned in the context of heparin, is the most abundantly occurring natural inhibitor of coagulation. It is a single-chain 432 amino acid glycoprotein displaying four oligosaccharide side chains and an approximate molecular mass of 58 kDa. It is present in plasma at concentrations of 150 pig ml 1 and is a potent inhibitor of thrombin (factor Ha), as well as of factors IXa and Xa. It inhibits thrombin by binding directly to it in a 1 1 stoichiometric complex. 

Subsequent investigations on the structure of heparin concentrated on the isolation and structural determination of larger oligosaccharides, in order to determine the structural elements involved in anti-blood-clotting activity associated with the binding to antithrombin. 

Effects of oligosaccharides on the biological functions of proteins (15 examples). The capacity for homophilic binding of the neural cell adhesion molecule (N-CAM, Section 12.5.3) is modulated by the extension of its polysialic chains. The binding of a highly specific heparin pentasaccharide sequence to the protein antithrombin III converts it to a potent anticoagulant (Section 17.3). 

A combination of n.m.r. spectroscopy and theoretical calculations was employed in conformational studies on the pentasaccharide (46) which represents the binding site of antithrombin on xylose-containing oligosaccharides, such as the tetrasaccharide (47), related to N-glycoproteins, and on the branched trisaccharides (48) for each of which a highly predominant (>90%) conformer was detected. 

A review on protective group strategies in carbohydrate synthesis has appeared which included consideration of the preparation of phosphate and sulphate esters of heparin oligosaccharides, and a related article covered the detailed consideration of the binding domains associated with the heparin-antithrombin 3 complex. ... 

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