ABSTRACT
The interaction of reducing agents with proteins is more complicated than the reduction of disul-de bonds. While there is some mention of disulde bond reduction in the current chapter, specic discussion of reduction of disulde bonds is presented in Chapter 8. A reducing agent can be used for the reduction of other oxidized forms of cysteine such as cysteine sulfenic acid or S-nitrosocysteine, the reduction of imine bonds in Schiff bases, the reduction of metal ion centers in proteins such as those found in heme proteins, and the reduction of pertechnetate (99mTcO4−) to product technetium (99mTc), which is then bound to reduced antibody or other ligand proteins for diagnostic use. In addition to the targets for reduction in protein chemistry, there are also a variety of reducing agents (see Table 6.1) whose function depends not just on intrinsic redox characteristics but the chemical structure being reduced. As an example, the selective reduction of disulde bonds has been used for the study of the relationship of protein structure to function1-4 as well as the importance of disulde bonds in providing stability for native conformation.5,6 Limited reduction of immunoglobulin proteins has proved useful for the determination of protein structure.7-11 Early work on the selective reduction of disulde bonds in immunoglobulin was part of the manufacturing process for a therapeutic intravenous immunoglobulin.12-14 More recently, as described in the succeeding text, monoclonal antibodies have been reduced and then modied with maleimide-based drugs for therapeutic purposes.15 Reducing agents are also used for the reduction of other cysteine oxidation products such as sulfenic acid.16,17 Lindhoud and coworkers17 observed that DTT could convert cysteine sulfenic acid or disuldes to cysteine but did not reduce either cysteine sulnic acid or cystine sulfonic acid. This provides a useful method for distinguishing between cysteine oxidation products.
