Biomaterial Database

Chemical modification and chemical cross-linking for protein/enzyme stabilization. 1998

R Tyagi, and M N Gupta

Chemistry Department, Indian Institute of Technology, Hauz Khas, New Delhi, 110016 India. mngupta@chemistry.iitd.ernet.in

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.

UI	MeSH Term	Description	Entries
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D011506	Proteins	Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.	Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D003432	Cross-Linking Reagents	Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.	Bifunctional Reagent,Bifunctional Reagents,Cross Linking Reagent,Crosslinking Reagent,Cross Linking Reagents,Crosslinking Reagents,Linking Reagent, Cross,Linking Reagents, Cross,Reagent, Bifunctional,Reagent, Cross Linking,Reagent, Crosslinking,Reagents, Bifunctional,Reagents, Cross Linking,Reagents, Cross-Linking,Reagents, Crosslinking
D004795	Enzyme Stability	The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat.	Enzyme Stabilities,Stabilities, Enzyme,Stability, Enzyme
D004798	Enzymes	Biological molecules that possess catalytic activity. They may occur naturally or be synthetically created. Enzymes are usually proteins, however CATALYTIC RNA and CATALYTIC DNA molecules have also been identified.	Biocatalyst,Enzyme,Biocatalysts
D013696	Temperature	The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.	Temperatures
D017510	Protein Folding	Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.	Protein Folding, Globular,Folding, Globular Protein,Folding, Protein,Foldings, Globular Protein,Foldings, Protein,Globular Protein Folding,Globular Protein Foldings,Protein Foldings,Protein Foldings, Globular