Hydroxyl group derivatization heparin

Figure 2. Epichlorohydrin-mediated N-acetylated heparin hydroxyl group derivatization reaction scheme.

Hydroxyl Group Derivatization. Epichlorohydrin Activation. One-half gram of N-acetylated heparin was dissolved in 10 mL of 1.0M Na2C03 solution. One milliliter of epichlorohydrin and either 1 mL of n-butylamine or 1 g of glycine or 2-aminoethyl hydrogen sulfate were added to the heparin solutions and allowed to react at 40°C for 5 h. Reaction schemes are illustrated in Figure 2. The hydroxyl-derivatized heparins were then dialyzed and freeze-dried. 

The hydroxyl group at the C6 position is more active than that at the C3 position and is, therefore, derivatized favorably. Figure 4 shows the sulfation as a common example of this type of reaction. When this type of reaction (Figure 4) is conducted on chitin, the end products behave like heparin, an anti-blood-clotting agent (Wolform and Shen-Han, 1959). 

This chapter focuses on the effects of anticoagulant activity caused by specific functional group derivatization of heparin, and on preliminary immobilization spacer group evaluations. The functional groups selected for immobilization are hydroxyl and carboxylic heparin groups. 

These results indicate that, under partial derivatization, the chemical nature of the derivatized end group is not critical to anticoagulant activity within the limited number of derivatizing agents tested however, the degree of derivatization is critical. Furthermore, both carboxylic and hydroxyl heparin groups can be utilized in heparin surface coupling reactions. 

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