* To whom correspondence should be addressed.
Received July 2, 1997
The protein function as well as its stability is governed by the amino acid sequence which in turn defines the collective noncovalent interactions leading to its specific conformation. Hence, it is not surprising that chemical modification with monofunctional and bifunctional reagents (the latter is called chemical cross-linking) causes structural changes (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) involving these twin approaches for protein stabilization. In the case of chemical modification, both surface hydrophilization and enhancing surface 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 mixtures, protein stability may depend upon the nature of the organic solvents. In the case of polyphenol oxidase and trypsin (at least), it is possible to choose "good" solvents on the basis of the Polarity index of the solvent.
KEY WORDS: protein stability, chemical modification, chemical cross-linking, amyloglucosidase, beta-galactosidase, glycogen phosphorylase, glycoproteins, glyceraldehyde-3-phosphate dehydrogenase, beta-glucosidase, catalase, acid phosphatase, lysozyme, penicillin G acylase, polyphenol oxidase, RNase, trypsin, chymotrypsin