CHEMICAL MODIFICATION AND CHEMICAL CROSS-LINKING FOR PROTEIN ENZYME STABILIZATION/

The protein function as well as its stability is governed by the amino acid sequence which in turn defines the collective noncovalent intera ctions leading to its specific conformation. Hence, it is not surprisi ng that chemical modification with monofunctional and bifunctional rea gents (the latter is called chemical crosslinking) causes structural c hanges (sometimes even subtle) which can result in significant changes in the stability. This review, while recapitulating the early lessons , analyses recent work (including work from authors' laboratory) invol ving these twin approaches for protein stabilization. In the case of c hemical modification, both surface hydrophilization and enhancing surf ace hydrophobicity are reported to have enhanced protein stability in different cases. For cross-linking, the nature, span, and position of the cross-link are important factors in the stabilization achieved. It is also pointed out that in the case of aqueous-organic cosolvent mix tures, protein stability may depend upon the nature of the organic sol vents. In the case of polyphenol oxidase and trypsin (at least), it is possible to choose ''good'' solvents on the basis of the polarity ind ex of the solvent.