Heparin-related molecules

In addition to gangliosides, heparin related molecules have also been shown to be involved in fibronectin mediated cell adhesion. Heparin binding sites have been described on many cell adhesion proteins e.g., fibronectin (25-26), laminin (27), and vitronectin... 

Due to the established cell adhesive activity of fibronectin, it is not surprising that fibronectin also is involved in the control of cell motility and cell shape. Via the phagokinetic track method, it has been shown that the motility of cells increases with added fibronectin (31) and we have recently shown that heparin related molecules augment the action of fibronectin in this system (31). In addition to the stimulatory activity of fibronectin on the motility of several cell types in vitro, fibronectin has also been shown to be involved in the migration of neural crest cells in ovo (37). 

Dicoumarol and related molecules are generally used over prolonged periods, whereas heparin is used over shorter periods. Hirudin has recently been approved for general medical use, while ancrod remains under clinical investigation. 

Synthetic heparin mimetics consisting of 20 monosaccharides (20-mers) exhibited antithrombotic activity similar to that obtained for heparin. However, the cross-reactivity of these compounds with PF4 prompted the exploration of related molecules structurally closer to heparin. 

Heparin and the closely related molecule heparan sulfate act as cofactors in AT III inhibition process by affording a 1000-fold increase in the rate at which AT III inhibits coagulation enzymes (9). In the absence of heparin, AT III is a relatively ineffective inhibitor of factor Xa and thrombin (kgssoc [factor Xa] = 2.6 x 10 ... 

Jones H, Paul W, Page CP The effects of heparin and related molecules on vascular permeability and neutrophil accumulation in rabbit skin. Br J Pharmacol 2002 135 469 79. 

Meyer and Schwartz, in a study of model compounds structurally related to heparin, showed that the hydrolytic release of sulfate under acid conditions from 2-amino-2-deoxy-D-glucose A -sulfate is more rapid than from D-glucose 6-0-sulfate. These workers also obtained a biologically inactive, nitroso derivative of heparin, and offered this as evidence for a sulfamic acid linkage in the molecule. Wolfrom, Shen and Summers prepared methyl 2-amino-2-deoxy-A-sulfo-tri-0-sulfo-(3-D-glucopyranoside dibarium salt, and found that, on heating a 3 X 10 M solution in 0.004 N hydrochloric acid, the A-sulfate is lost in 20 minutes and the 0-sulfate after 12 hours. 

The mechanism whereby heparin functions as an anticoagulant, and the architectural features of the molecule which are associated with the activity, have not beeii fully elucidated. In the following Sections, an attempt has been made to integrate and evaluate the work done to date on the structure of heparin in relation to its activity. The suggestions subsequently made are not necessarily the only interpretations of the knowm data. 

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