Protecting the Native Conformation and Activity of Proteins

The goal of most protein modification or conjugation procedures is to create a stable product with good retention of the native state and activity. Ideally, any derivatization should result in a protein that performs exactly as it would in its unmodified form, but with the added functionality imparted by whatever is conjugated to it. Thus, an antibody molecule tagged with a fluorophore should retain its ability to bind to antigen and also have the added functionality of fluorescence. 

One of the best ways to ensure retention of activity in protein molecules is to avoid doing chemistry at the active center. The active center is that portion of the protein where ligand, antigen, or substrate binding occurs. In simpler terms, the active center (or active site) is that part that has specific interaction with another substance (Means and Feeney, 1971). For the preparation of enzyme derivatives, it is important to protect the site of catalysis where conversion of substrate to product happens. For instance, when working with antibody molecules, it is crucial to stay away from the two antigen binding sites. 

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