Disulfide interchange

Thiol—Disulfide Interchange Reactions. The interchange between thiols and disulfides has been reviewed (50). This reaction is base-catalyzed. It involves the nucleophihc attack of a thiolate ion on a disulfide. This is shown in equations 35, 36, and 37. 

Cystinuria. Penicillamine reduces excess cystine excretion in cystinuria. Penicillamine with conventional therapy decreases crystalluria and stone formation, and may decrease the size of or dissolving existing stones. This is achieved by disulfide interchange between penicillamine and cystine, resulting in a substance more soluble than cystine and readily excreted. 

Figure 1.73 The disulfide group of a cystamine-modified protein may undergo disulfide interchange reactions with another sulfhydryl-containing protein to yield a disulfide-linked conjugate.

The 4,4 -dipyridyl disulfide can be used in aqueous solutions, but it has been found that modification of proteins with this reagent yields rapid disulfide bond formation. Only when 2-iminothiolane is used in tandem with 4,4 -dipyridyl disulfide can 4-dithiopyridyl groups be introduced into proteins (King et al., 1978) (Section 4.1, this chapter). This is due to disulfide interchange reactions predominating without the addition of 2-iminothiolane. 

Figure 21.10 Cystamine may be used to make immunotoxin conjugates by a disulfide interchange reaction. Modification of antibody molecules using an EDC-mediated reaction creates a sulfhydryl-reactive derivative. A-chain toxin subunits containing a free thiol can be coupled to the cystamine-modified antibody to form disulfide crosslinks.

DISULFIDE INTERCHANGE AND ITS AVOIDANCE DURING THE SYNTHESIS OF PEPTIDES CONTAINING CYSTINE... 

The synthesis of peptides containing cystine is rarely performed starting with derivatives of cystine because of the obstacle of disulfide interchange. Disulfide interchange was discovered by F. Sanger during his attempts to determine the primary... 

FIGURE 6.22 Disulfide interchange.92 (A) Discovered in synthesis when hydrazinolysis of an unsymmetrical derivative of cystine gave two symmetrical products instead of the expected monohydrazide at the urethane-protected cysteine moiety of the derivative.95 (B) Mechanism for interchange catalyzed by strong acid,94 which is suppressed by thiols. (C) Mechanism for interchange catalyzed by weak alkali, which is enhanced by thiols. 

AP Ryle, F Sanger. Disulfide interchange reactions. Biochem J 535, 1955. 

RE Benesch, R Benesch. The mechanism of disulfide interchange in acid solution role of sulfenium ions. J Am Chem Soc 80, 1666, 1958. 

L Zervas, L Benoiton, E Weiss, M Winitz, JP Greenstein. Preparation and disulfide interchange reactions of unsymmetrical open-chain derivatives of cystine. J Am Chem Soc 81, 1729, 1959. 

Fig. 3. Inactivation of S-protein, by disulfide interchange in the absence, and subsequent reactivation in the presence, of S-peptide. The reaction was carried out with...

Keire, D.A., Strauss, E., Guo, W., Noszal, B., Rabenstein, D.L. Kinetics and equilibria of thiol/disulfide interchange reactions of selected biological thiols and related molecules with oxidized glutathione. J. Org. Chem. 1992, 57, 123-127. 

Shaked, Z. Szajewski, R. R Whitesides, G. M. Rates of thiol-disulfide interchange reactions involving proteins and kinetic measurements of thiol pKa values. Biochemistry 1980,19,4156-4166. 

This method is of use in thiol-disulfide interchanges and when using two-protonic-state electrophiles. ... 

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