Thiol interchange

Thioamide formation benzodiazepinone, 505 heteiodiazepinone, 621 phosphorus pentasulf ide, 323, 600 Thioazole formation, nitrile addition, 301 Thiocarbamate formation, 588 phenol, 95 rearrangement, 517 Thioenol ether formation, 185, 517 addition-elimination, 554 Thioester formation, mixed anhydride, 184 Thioether formation, 241, 300, 413, 416 alkylation, 586, 588 aromatic displacement, 416 Thiohydantoin formation, 293 Thiol interchange, benzothiazole formation, 422... 

This is illustrated in Fig. 6 for the reaction of succinyl CoA acetoacetate coenzyme A transferase with its specific substrate succinyl CoA, compared with the corresponding nonenzymic reaction through the transition state [34]. Both reactions involve thiol interchange to form a new thiol ester of coenzyme A. Catalysis by the enzyme increases the reaction rate by a factor of 5 x 10, which corresponds to a stabilization of the transition state by 18.7 kcal moP Most of this stabilization arises from the utilization of noncovalent binding interactions between the coenzyme A moiety of the substrate and the enzyme. A short chain thiol ester of succinate with methyl mercaptopropionate has the same chemical properties as succinyl CoA but lacks the specific binding groups of the normal substrate this compound reacts with the enzyme some 10 more slowly than succinyl CoA, only an order of... 

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. 

In addition to its role as the P-subunit of PHY, PDI acts independently by catalysing thiol/protein disulphide interchange. The role of PDI as the P-subunit in prolyl 4-hydroxylase is not related to its disulphide isomerase activity and experiments where the vertebrate PDI was mutated in both thioredoxin-like active domains had no effect on tetramer assembly (Vuori et al., 1992). PDI appears to function as a molecular chaperone, retaining the a-subunits in the correct catalytically active, non-aggregated form in the ER-lumen (John et al, 1993). Dissociation of the P-subunits results in insoluble aggregates of the a-subunits, analogous to a-subunits expressed in the absence of PDI. An additional function of PDI in the complex is to maintain the ER luminal location of the a-subunits, since deletion of the ER retention signal from PDI results in the secretion of the complex (Vuori et al., 1992). 

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.

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. 

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. ... 

Racemic thioglycerol (3-sulfanylpropane-l,2-diol) was used for the attachment of two lipid chains via ester bond formation with the hydroxy groups 82 while the free thiol group serves for selective cross-linking to other molecules via disulfide or sulfide bonds utilizing mild thiol-disulfide interchange or thiol addition reactions (Scheme 15).[163,164,167]... 

Thiols can be linked to insoluble supports as disulfides by disulfide interchange. Mixed disulfides can be prepared on insoluble supports by treating support-bound thiols with excess activated disulfide (e.g. 2-benzothiazolyl, 2-nitrophenyl, 3-nitro-2-pyridyl disulfides [60,676] or a methanethiosulfonate MeS02-SR [677] Figure 3.33), or by treating a support-bound disulfide (e.g. a 2-pyridyl disulfide [191]) with a thiol. Resin-bound disulfides are stable under the conditions of standard Fmoc peptide synthesis, but can be cleaved by reducing agents (Entries 8 and 9, Table 3.37 [191,676,678-681]). 

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