Disulfide isomerization

Ahamed, J., Versteeg, H.H., Kerver, M., Chen, V.M., Mueller B.M., Hogg, P.J., and Ruf, W. (2006) Disulfide isomerization switches tissue factor from coagulation to cell signaling. Proc. Natl. Acad. Sci. 103,13932-13937. 

Protein disulfide isomerase and PDI related proteins Foldase, Chaperone Disulfide formation, disulfide isomerization, folding pdiA tigA prpA... 

VIII. Disulfide Bond Formation Does Not Interfere with Disulfide Isomerization 298... 

Future work on the two disulfide isomerases DsbC and DsbG might show how these proteins interact with their native substrate proteins. It is of great interest to identify particular in vivo substrates for these catalysts. The interaction of DsbC and DsbG with their native substrates can then be studied in vivo and in vitro, and in conjunction with structural information, might lead to a better understanding of the mechanisms that drive disulfide isomerization. 

Thiol-disulfide isomerization. Disulfide bond formation between Cys residues takes place commonly in the ER during protein biosynthesis. The thiol-disulfide isomerization can occur by either chemical exchange reaction or enzymatic reaction catalyzed by protein disulfide isomerase via mixed disulfide intermediate (protein-S-SG). 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Sodium or potassium hydrogen sulfite reacts with several thiiranes to give disulfides of /3-mercaptosulfonic acid salts (76EGP122086). Potassium thiocyanate in dimethylformamide or aqueous ethanol isomerizes thiiranes (Scheme 84) (72CJC3930). 1,2-Dithiols are obtained by treatment of thiiranes with NaBH2S3 obtained from sodium borohydride and sulfur (73TL1401). 

Enzymes assist formation of proper disulfide bonds during folding Isomerization of proline residues can be a rate-limiting step in protein folding Proteins can fold or unfold inside chaperonins GroEL is a cylindrical structure with a... 

Both CSs and CSs were also successfully generated by the fragmentation of ionized 4,5-dioxo-2-thioxo-l,3-dithione (65) and 2-thioxo-l,3-dithiole (66) (90JA3750). Tire three sulfur atoms in the anion and cation radicals were chemically equivalent, suggesting that they take the D h (or C2u) form (67 or 68). On the other hand, under similar conditions, 3-thioxo-1,2-dithiole (69) yielded two isomeric cation radicals the (or 2 ) form and the carbon disulfide 5-sulfide form (70). Ab initio calculations on three electronic states of CS3 at the 6-31G -l-ZPVE level indicated that the C21, form (68) was more stable than the carbon disulfide 5-sulfide form (70) in the neutral (both singlet and triplet states) and the anion radical states, but 68 was less stable than 70 in the radical cation state. 

Ajoene (Spanish, ajo, garlic), 4,5,9-trithiadodeca-l,6,ll-triene-9-oxide 35 (Scheme 12), an antithrombotic compound with other well-defined physiological properties, is formed from allicin.84 Like allicin, ajoene is a sulfoxide but has two further sulfur atoms in a disulfide linkage. E and Z isomeric forms are possible involving the C=C bond at positions 6 and 7. Ajoene is somewhat more stable than allicin. The formation of ajoene probably involves condensation of 2 molecules of allicin forming a sulfonium salt 33, with elimination of propenesulfenic acid. Elimination of a second molecule of propenesulfenic acid... 

Oxidation Disulfide exchange Isomerization Photo decompo sition... 

One of the most studied functions of PDI is its ability to catalyze isomerization and rearrangement of disulfide bonds (Eq. (14)) in the ER contributing to a proper folding of nascent proteins (Novia et al., 1992). 

Condensation of 1-amino-1-deoxy-D-fructose with carbon disulfide in the presence of excess triethylamine at 5 °C, leading to a (5/ )/(5.S )-diastereo-isomeric mixture of open-chain l,3-thiazolidine-2-thiones, was reported in 1975 by Jochims (Scheme 15).39... 

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