Thiol/disulfide exchange

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. 

The second activity, termed denitrosation (Eq. (15)), is catalyzed by the reduced form of the same active site thiols that are involved in the thiol-disulfide exchange activity of the enzyme (Zai et al, 1999 Ramachandran et al. 2001 Raturi and Mutus, 2004). In this process csPDI catalyzes the release of NO from RSNOs. 

Scheme 7.3 (a) Anchor fragments equipped with two thiol moieties (F-J). (b) Thiol partner fragments (4-22). (c) DCC ntilizing thiol-disulfide exchange and targeting metallo-P-lactamase (Bell). 

Fig. 10 Covalent immobilization of ssDNA by thiol/disulfide exchange reaction between disulfide-modified oligonucleotides and mercapto-modified substrates...

Drugs coupled via a disulfide bond like, captopril, are rapidly released from the protein-spacer moiety of the conjugate, enzymatically by 3-lyase and/or non-enzymatically by thiol-disulfide exchange with endogenous thiols [68]. 

Mechanism of Action Asulfhydryl compound with similar properties to those of penicillamine and glutathione that undergoes thiol-disulfide exchange with cysteine to form tiopronin-cysteine, a mixed disulfide. This disulfide is water soluble, unlike cysteine, and does not crystallize in the kidneys. May break disulfide bonds present in bronchial secretions and break the mucus complexes. Therapeutic Effect Decreases cysteine excretion. 

These early studies clearly revealed the inherent problems of the chemistry for site-directed formation of unsymmetrical disulfides that has to avoid formation of homodimers. These can result from (i) slow rates of activation of the cysteine peptide, (ii) disproportionation of the activated cysteine species, (in) weak activation and thus slow thiolysis by the second cysteine component and thus its oxidation to the homodimer as well as thiol/ disulfide exchange reactions on the unsymmetrical disulfide present in the reaction media. The latter side reactions are partly controlled by operating in degassed argon-saturated buffers or in organic solvents and preferably under acidic conditions where thiol/disulfide exchange reactions on the nonactivated disulfides, i.e. on the target unsymmetrical cystine peptide occurs at slow rates. 

Dupont E, Aoumari A, Briand JP, Fromaget C, Gros D Cross linking of cardiac gap junction connexons by thiol/disulfide exchanges. J Membr Biol 1989 108 247-252. 

Bowen, W.K., Hellewell, S B., Keleman, M., Huey, R., Stewart, D. Affinity labelling of 6-opiate receptors using [D-Ala2, Leu5, Cys6]enkephalin covalent attachment via thiol-disulfide exchange, J. Biol. Chem. 1987, 262, 13434-13439. 

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