Exchange disulfide

Disulfide bonds between and within polypeptides stabilize tertiary and quaternary structure. However, disulfide bond formation is nonspecific. Under oxidizing conditions, a given cysteine can form a disulfide bond with the —SH of any accessible cysteinyl residue. By catalyzing disulfide exchange, the rupture of an S— bond and its reformation with a different partner cysteine, protein disulfide isomerase facilitates the formation of disulfide bonds that stabilize their native conformation. 

Disruption of the native structure of a protein can also contribute to chemical instability by accelerating the rates of a variety of degradation routes, including deamidation, hydrolysis, oxidation, disulfide exchange, /1-elimination, and racemization. 

Using this approach, EGF has been successfully conjugated by disulfide exchange to the A chain of diphtheria toxin (Shimisu et al., 1980). A cystaminyl derivative of insulin also could be conjugated to the A chain of diphtheria toxin by this method (Miskimins and Shimizu, 1979). Other references to disulfide exchange using cystamine include Oeltmann and Forbes (1981) and Bacha et al. (1983) who prepared antibody-toxin and peptide-toxin conjugates, respectively. 

Disulfide exchange reactions occur over a broad range of conditions—from acid to basic pH—and in a wide variety of buffer constituents. Most crosslinking reactions involving disulfide exchange are done under physiological conditions or those most appropriate to maintain stability of the protein or other molecule being modified. 

Preparation of Immunotoxin Conjugates via Disulfide Exchange Reactions... 

Simanek el al. investigated the structure dependence of the kinetics of thiol-disulfide exchange reactions.[44] In general, the rate of exchange decreased as the size of the dendrimers increased. Dendrimers with disulfides attached near the core undergo exchange more slowly than dendrimers with disulfides at the periphery. No evidence was found for intramolecular macrocyclization (cooperative) exchange. 

Oxidation Disulfide exchange Isomerization Photo decompo sition... 

Disulfide exchange can also sometimes occur, and prompt a reduction in biological activity (Figure 6.21). Intermolecular disulfide exchange can result in aggregation of individual polypeptide molecules. 

Figure 6.21 Diagram representing the molecular process of intrachain (a) and interchain (b) disulfide exchange. Refer to text for specific details. (—0— are amino acid residues in the polypeptide)...

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