Polyaldehyde dextran

Figure 25.12 Dextran polymers can be oxidized with sodium periodate to create a polyaldehyde derivative. Note that additional oxidation may occur to cleave off another carbon atom and create an aldehyde on the adjacent C—OH group.

Figure 25.13 Polyaldehyde dextran may be used as a multifunctional crosslinking agent for the coupling of amine-containing molecules. Reductive amination creates secondary amine or tertiary amine linkages.

The following protocol for creating the polyaldehyde dextran derivative is based on the method of Bernstein et al. (1978). 

Remove excess reactant by extensive dialysis against water. The purified polyaldehyde dextran may be lyophilized for long-term storage. 

Prepare polyaldehyde dextran according to the method of Section 2.1 (this chapter). 

Dissolve polyaldehyde dextran in the ethylene diamine (or adipic dihydrazide) solution at a concentration of 25 mg/ml. 

Figure 25.19 Polyaldehyde dextran may be modified with the hydrazide end of M2C2H to create a thiol-reactive polymer.

Heindel, N.D., Zhao, H., Leiby, J., VanDongen, J.M., Lacey, C.J., Lima, D.A., Shabsoug, B., and Buzby, J.H. (1990) Hydrazide pharmaceuticals as conjugates to polyaldehyde dextran Syntheses, characterization, and stability. Bioconjugate Chem. 1, 77-82. 

Zhao, H., and Heindel, N.D. (1991) Determination of degree of substitution of formyl groups in polyaldehyde dextran. Pharm. Res. 8, 400M02. 

Figure 386 Dextran polymers may be oxidized with sodium periodate to create a polyaldehyde derivative.

Several chemical approaches may be used to form the amine- or carboxyl-terminal dextran derivative. The simplest procedure may be to prepare polyaldehyde dextran according to the procedure of Section 2.1, and then make the spacer arm derivative by reductively animating an amine-containing organic compound onto it. For instance, short diamine compounds such as ethylene diamine or diaminodipropylamine (3,3 -iminotepropylamine) can be coupled in excess to polyaldehyde dextran to create an amine-terminal derivative. Carboxyl-terminal derivatives may be prepared similarly by coupling molecules such as 6-aminocaproic acid or p-alanine to polyaldehyde... 

Reduced dextran dialdehydes. The reaction of dextran (D-OH) with sodium metaperiodate is a two step reaction leading to different kinds of aldehyde functions. Although the aldehyde content can not be precisely predicted from the amount of periodate added, by approximation 1.5 equivalents of periodate are required per dialdehyde structure. By varying the amount of periodate added to the polysaccharide dextran dialdehydes with variable degree of oxidation were obtained. In order to avoid interaction of the polyaldehyde (D-CH=0) with the dextranases the aldehyde groups were subsequently reduced by reaction with sodium borohydride ... 

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