Reductive amination conjugation

Aldehydes and ketones are converted to amines by a handful of methods. The most common is reductive amination. When a keto-acid or keto-ester molecule is utilized and the carbonyl is not in conjugation, reductive amination leads to an amino acid or an amino-ester. When the carbonyl of an aldehyde or ketone is P- to the carboxyl moiety, reductive amination is unnecessary for preparing amino acids and alkenyl amino acids are possible (specifically, 3-aminopropenoic acid derivatives). There are several methods that can be applied to keto-acid derivatives, largely dependent on whether the aldehyde or ketone carbonyl is in or out of conjugation with the carboxyl moiety. The first part of this section will focus on reductive amination procedures, and the latter part of the section will focus on p-keto acids and esters. A few other specialized methods for converting aldehydes and ketones to amino acids will be mentioned at the end of this section. l.l.C.1. Reductive Amination... 

Figure 7.11 Oxidation of glycoproteins with periodate, such as glycosylated antibodies, results in the formation of aldehyde groups that can be used for conjugation to dendrimers containing amine groups. Reductive amination with sodium cyanoborohydride results in coupling via secondary (or tertiary) amine bonds.

Figure 7.15 The reducing end of a glycan or a carbohydrate can be used to conjugate to an amine-dendrimer by reductive amination, which results in the formation of a secondary amine linkage.

Reductive Amination-Mediated Hapten-Carrier Conjugation... 

A second method of immunotoxin preparation by reductive amination involves the use a polysaccharide spacer. Soluble dextran may be oxidized with periodate to form a multifunctional crosslinking polymer. Reaction with antibodies and cytotoxic molecules in the presence of a reducing agent forms multivalent immunotoxin conjugates. The following sections discuss these options. 

Conjugation via Periodate Oxidation Followed by Reductive Amination... 

Conjugation of HRP by reductive amination can be done by oxidizing the carbohydrate on the enzyme and subsequently coupling to the amines on (strept)avidin (Figure 23.5). 

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