chapter  7
122 Pages

Chemical Modication of Cysteine

There are a variety of reagents available for the modication of cysteinyl residues in proteins (Table 7.1; Figure 7.1), which vary in their chemistry including reaction rate (Figure 7.2), solution behavior, and physical size. As such, it is important to determine the purpose of modication of cysteine prior to selection of a reagent and establishment of experimental conditions. The chemical modication of cysteine residues can proceed via a nucleophilic addition or displacement reaction with the thiolate anion as the nucleophile (Figure 7.2). The reaction with the α-ketohaloalkyl compounds such as iodoacetate is an example of a nucleophilic displacement reaction (SN2 reaction), while the reaction of maleimide is a nucleophilic addition to an olen (Michael reaction). Disuldeand disulde-like compounds such as the methylthiosulfonates react with cysteine to form mixed disuldes. The haloalkyl compounds, maleimides, and alkyl alkanethiosulfonates are also base structures for more complex molecules such as spectral probes and cross-linking agents, which are discussed elsewhere in the text. Metal ions such as mercuric can react with cysteine to form a presumably covalent derivative, while zinc ions form a less stable linkage; gold and silver are thought to form a covalent bond with cysteinyl residues. Many of the reagents used to modify cysteine residues are alkylating agents which are discussed in Chapter 2.