Protein side chain groups, reactions

Although effects of hydration are important in almost all biochemical equilibria, they are difficult to assess quantitatively. It is hard to know how many molecules of water are freed or immobilized in a given reaction. Charged groups in proteins are often hydrated. However, if they are buried in the interior of the protein, they may be solvated by polarizable protein side chain groups such as -OH or by backbone or side chain amide groups.57 58... 

Figure 4.33 Benzidine can be diazotized with sodium nitrite and HC1 for reaction with proteins through their tyrosine, histidine, or lysine side-chain groups.

In addition to the stable isotope labeling ( 0 versus 0) of proteins for quantifiable proteomic analyses as described above, chemical approaches to the protein-labeUng problem have developed in great variety. These so-called affinity tags can be used to label specific side chain groups such as sulfhydryl or amino groups, active sites for serine and cysteine hydrolases and many others. This active research area has been reviewed recently by A. Leitner and W. Lindner in a Proteomics article entitled Chemistry meets proteomics The use of chemical tagging reactions for MS-based proteomics. ... 

In addition, we can meet examples of covalent bonding that are responsible for binding a substrate, where a functional group in the substrate reacts chemically with a protein side-chain functional group. Two important reactions are ... 

The reaction of IODO-GEN with iodide ion in solution results in oxidation with subsequent formation of a reactive, mixed halogen species, IC1 (Fig. 266). Either 125I or 13 1 can be used in this reaction. The IC1 then rapidly reacts with any sites within target molecules that can undergo electrophilic substitution reactions. Within proteins, any tyrosine and histidine side-chain groups can be modified with iodine within... 

For certain reactions, such as acid-base catalysis, reactivity of up to 105 over background was demonstrated with serum albumins, ordinary off-the-shelf proteins without any designated catalytic activity but with a lysine side chain group acting as a general base. 

Approximately 150 different amino acid residues have been reported in proteins (1 5). At least half of these could undergo chemical deteriorations under the conditions of stress usually encountered. Many of these deteriorative reactions involve hydrolytic scissions, not only of peptide bonds but of the many different nonprotein substances added covalently to proteins postribosomally. These susceptible side chain groups are indole, phenoxy, thioether, amino, imidazole, sulfhydryl, and derivatives of serine and threonine (such as 0-glycosyl or O-phosphoryl), the disulfides of cystine, and, of course, the amides (such as asparagine and glutamine). With strong acid or alkali, other residues, such as serine and threonine, also are less stable. 

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