Primary side, modification reactions

In summary, protein molecules may contain up to nine amino acids that are readily derivatizable at their side chains aspartic acid, glutamic acid, lysine, arginine, cysteine, histidine, tyrosine, methionine, and tryptophan. These nine residues contain eight principal functional groups with sufficient reactivity for modification reactions primary amines, carboxylates, sulfhydryls (or disulfides), thioethers, imidazolyls, gua-nidinyl groups, and phenolic and indolyl rings. All of these side chain functional groups in addition to the N-terminal a-amino and the C-terminal a-carboxylate form the full complement of polypeptide reactivity within proteins (Fig. 12). 

The primary polyphosphazene synthesis processes discussed above provide access to an enormous variety of different macromolecules. Yet further structural diversity can be achieved by carrying out modification reactions on the organophosphazene polymers produced in these primary rections. Secondary reactions are particularly important for the preparation of polymers with functional units in the side group structure, species that would be difficult or impossible to produce by the primary synthesis methods. 

Primary amine groups on proteins consisting of N-terminal a-amines and lysine side-chain e-amines are typically present in abundant quantities for modification or conjugation reactions. Occasionally, however, a protein or peptide will not contain sufficient amounts of available amines to allow for an efficient degree of coupling to another molecule or protein. For instance, horseradish peroxidase (HRP), a popular enzyme to employ in the preparation of antibody conjugates, only possesses two free amines that... 

In the analysis of proteins in forensic applications, the chemical modifications that occur to proteins, posttranslationally and nonenzymatically, are of primary importance. These chemical changes are a result of chemical reactions between side chains of the protein and reactive groups of metabolites and/or exogenous toxicants, including drugs present in extracellular fluid such as serum. The analytical accessibility of these modified proteins depends on their rate of turnover. For example, those with a slow turnover rate will be long-lived, and such problems will be much more easy to identify than those with faster turnover rates. 

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